CA2071102A1 - Process for the preparation of 1-alkoxy-2-dialkylaminoethanes - Google Patents
Process for the preparation of 1-alkoxy-2-dialkylaminoethanesInfo
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- CA2071102A1 CA2071102A1 CA 2071102 CA2071102A CA2071102A1 CA 2071102 A1 CA2071102 A1 CA 2071102A1 CA 2071102 CA2071102 CA 2071102 CA 2071102 A CA2071102 A CA 2071102A CA 2071102 A1 CA2071102 A1 CA 2071102A1
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- Prior art keywords
- process according
- alkali metal
- carried out
- distillation
- alkoxy
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
Abstract
ABSTRACT
1-Alkoxy-2-dialkylaminoethanes of the formula
1-Alkoxy-2-dialkylaminoethanes of the formula
Description
2~7~ 1~2 H~LS ARTI~NG~S~LLSCHAFT - 1 -- PAT%NT DEPARTMENT - O.Z. 4594 Process for the preparation of L-alkoxy-2-dialkylamino-ethanes The invention relates to a process for the preparation of 1-alkoxy-2-dialkylaminoethanes of the general formula S (III) from ~-dialkylaminoethano:L (I) and alkyl hal~de~
F~-X (II) R~ Rl N - CH2~ - CH2 - 0~ ~11 - C~2 - C~2 - - Q2 Rl (~) (III) Rl = alkyl C1-C10, preferably Cl to C3, R~ = alkyl Cl-C10, identical to or different from Rl, preferably C1 to C3, and X = Cl, Br or I, characterised in that a) ~-dialkylaminoethanol (I) is reacted with sodium alkoxides or potassium alkoxides of simple alcohols, preferably methanol, with total removal of the simple alcohol, b) the dialkylaminoethanol (I) is used in an excess of 0.1 to 30, preferably 5 to 20 mol%, relative to the alkali metal alkoxide, c) the total removal of the simple alcohol is carried out by distillation with inert solvents such as aliphatic or aromatic hydrocarbons, but preferably with the 1-alkoxy-2-dialkylaminoethane itself to be prepared, d) the reaction of the alkali metal ~-dialkylamino-ethoxide formed according to a) to c) is carried out with alkyl halides, preferably with alkyl chlorides, at elevated temperatures and at atmospheric pressure or elevated pressure, e) the distillation of the pure target product 1-alkoxy-2-dialkylaminoethane is carried out with prior addition of Na/R alkoxide, f) these Na/R alkoxides according to e) are added in 2~7~ 1~2 amounts which are at least stoichiometrically equivalent to the residual dialkylaminoethanol, but preferably are employed in an excess of up to 15 mol~, g) this alkali metal ~-dialkylaminoethoxide remaining in the bottom of the distillation of the pure product is converted in the alkylation reaction of the following batches.
l-Alkoxy-2-dialkylaminoethanes have been known for a long time. They were prepared by reaction of 2-dimethylamino-ethyl chloride with sodium methoxide. The reaction and working-up conditions without yield data found therein are difficult and result in low purity.
According to U. S. Patent 4,588,843, the alkali metal alkoxide formation from ~-dialkylaminoalkanol is carried out using NaOH/KOH and the subsequent reaction using alkyl halides.
Working-up from an aqueous phase by extraction with ether is troublesome and results in only 37~ yield.
The object for the preparation of l-alkoxy-2-dialkyl-aminoethane was a technically simple process by which the target product is obtained in high yields and purities.
Thus, according to one aspect, the invention provides a process for the preparation of a l-alkoxy-2-dialkylaminoethane of the formula ~III):
\ N - CH2 - CH2 R2 (III) Rl wherein Rl and R2 represent a Cl-Cl0-alkyl, which process comprises:
~7~:~a~
- 2a -a) reacting ~-dialkylaminoethanol of the formula (I):
\ N - CH2 - CH2 - OH (I) wherein Rl is as defined above, with an alkali metal alkoxide of a simple alcohol, with total removal of the simple alcohol, b) reacting the alkali metal ~-dialkylaminoethoxide so obtained with an alkyl halide of the formula (II):
R2 - X (II) wherein R2 is as defined above and X is Cl, Br or I, and c) recovering the l-alkoxy-2-dialkylaminoethane so obtained.
According to this invention, the process starts from ~-dialkylaminoethanol, a product which is simple to prepare on a large scale from ethylene oxide and dialkylamines.
This ~-dialkylamino alcohol must be converted quantitatively into its alkali metal alkoxide, which is carried out according to the invention using alkali metal alkoxides. The sodium alkoxides and potassium alkoxides of short-chain alcohols having 1 to 3 C atoms are preferred, particularly sodium methoxide. The alkoxide as a solution in the respective alcohol or alternatively as 2~ 71 l 0~?
F~-X (II) R~ Rl N - CH2~ - CH2 - 0~ ~11 - C~2 - C~2 - - Q2 Rl (~) (III) Rl = alkyl C1-C10, preferably Cl to C3, R~ = alkyl Cl-C10, identical to or different from Rl, preferably C1 to C3, and X = Cl, Br or I, characterised in that a) ~-dialkylaminoethanol (I) is reacted with sodium alkoxides or potassium alkoxides of simple alcohols, preferably methanol, with total removal of the simple alcohol, b) the dialkylaminoethanol (I) is used in an excess of 0.1 to 30, preferably 5 to 20 mol%, relative to the alkali metal alkoxide, c) the total removal of the simple alcohol is carried out by distillation with inert solvents such as aliphatic or aromatic hydrocarbons, but preferably with the 1-alkoxy-2-dialkylaminoethane itself to be prepared, d) the reaction of the alkali metal ~-dialkylamino-ethoxide formed according to a) to c) is carried out with alkyl halides, preferably with alkyl chlorides, at elevated temperatures and at atmospheric pressure or elevated pressure, e) the distillation of the pure target product 1-alkoxy-2-dialkylaminoethane is carried out with prior addition of Na/R alkoxide, f) these Na/R alkoxides according to e) are added in 2~7~ 1~2 amounts which are at least stoichiometrically equivalent to the residual dialkylaminoethanol, but preferably are employed in an excess of up to 15 mol~, g) this alkali metal ~-dialkylaminoethoxide remaining in the bottom of the distillation of the pure product is converted in the alkylation reaction of the following batches.
l-Alkoxy-2-dialkylaminoethanes have been known for a long time. They were prepared by reaction of 2-dimethylamino-ethyl chloride with sodium methoxide. The reaction and working-up conditions without yield data found therein are difficult and result in low purity.
According to U. S. Patent 4,588,843, the alkali metal alkoxide formation from ~-dialkylaminoalkanol is carried out using NaOH/KOH and the subsequent reaction using alkyl halides.
Working-up from an aqueous phase by extraction with ether is troublesome and results in only 37~ yield.
The object for the preparation of l-alkoxy-2-dialkyl-aminoethane was a technically simple process by which the target product is obtained in high yields and purities.
Thus, according to one aspect, the invention provides a process for the preparation of a l-alkoxy-2-dialkylaminoethane of the formula ~III):
\ N - CH2 - CH2 R2 (III) Rl wherein Rl and R2 represent a Cl-Cl0-alkyl, which process comprises:
~7~:~a~
- 2a -a) reacting ~-dialkylaminoethanol of the formula (I):
\ N - CH2 - CH2 - OH (I) wherein Rl is as defined above, with an alkali metal alkoxide of a simple alcohol, with total removal of the simple alcohol, b) reacting the alkali metal ~-dialkylaminoethoxide so obtained with an alkyl halide of the formula (II):
R2 - X (II) wherein R2 is as defined above and X is Cl, Br or I, and c) recovering the l-alkoxy-2-dialkylaminoethane so obtained.
According to this invention, the process starts from ~-dialkylaminoethanol, a product which is simple to prepare on a large scale from ethylene oxide and dialkylamines.
This ~-dialkylamino alcohol must be converted quantitatively into its alkali metal alkoxide, which is carried out according to the invention using alkali metal alkoxides. The sodium alkoxides and potassium alkoxides of short-chain alcohols having 1 to 3 C atoms are preferred, particularly sodium methoxide. The alkoxide as a solution in the respective alcohol or alternatively as 2~ 71 l 0~?
- 3 - O.Z. 4594 the isolated salt i~ additionally preferred.
The alkali metal alkoxides are employed in a sub-equiva-lent amount to the ~-dialkylaminoethanol (I), at most in stoichiometrically equivalent amounts. The formation of the alkali metal salt of th~e ~-dialkylaminoethanol thereby takes place more rapidly and more simply, and no residual alkali metal alkoxide solution remains, which would Lmmediately form low-boiling alkyl ethers with the alkyl halide.
The molar excess of (I) is 0.1 to 30~, preferably 5 to ( 20%, and is later bound in the distillation of the pure product as alkali metal salt, as i~ still to be explained.
The difficulty in this process is the total removal of the short-chain alcohol, i.e. in the quantitative conver-sion into the sodium ~-dialkylaminoethoxide. Thi~ is achieved by entraining the methanol by distillation with an inert solvent, it also being possible for this solvent to form an azeotrope with methanol, for example toluene, xylene, alkanes having 5 to 8 C atoms such as hexane, heptane, cyclohexane or t-butyl methyl ether. Because of the difficulties of recovering this solvent, i.e. the separation of the methanol, the target product, i.e. the respective l-alkoxy-2-dialkylaminoethane is preferably employed, in particular after the second or third batch.
The use of this not 80 pure final product has the great advantage that no independent solvent subsequently has to be worked up, i.e. separated from methanol, and the purity of the final product cannot be contaminated by traces of the independent solvent.
Furthermore, the solubility of the alkali metal ~-dialkylaminoethoxide therein is better than in an extraneous solvent.
2 ~
The alkali metal alkoxides are employed in a sub-equiva-lent amount to the ~-dialkylaminoethanol (I), at most in stoichiometrically equivalent amounts. The formation of the alkali metal salt of th~e ~-dialkylaminoethanol thereby takes place more rapidly and more simply, and no residual alkali metal alkoxide solution remains, which would Lmmediately form low-boiling alkyl ethers with the alkyl halide.
The molar excess of (I) is 0.1 to 30~, preferably 5 to ( 20%, and is later bound in the distillation of the pure product as alkali metal salt, as i~ still to be explained.
The difficulty in this process is the total removal of the short-chain alcohol, i.e. in the quantitative conver-sion into the sodium ~-dialkylaminoethoxide. Thi~ is achieved by entraining the methanol by distillation with an inert solvent, it also being possible for this solvent to form an azeotrope with methanol, for example toluene, xylene, alkanes having 5 to 8 C atoms such as hexane, heptane, cyclohexane or t-butyl methyl ether. Because of the difficulties of recovering this solvent, i.e. the separation of the methanol, the target product, i.e. the respective l-alkoxy-2-dialkylaminoethane is preferably employed, in particular after the second or third batch.
The use of this not 80 pure final product has the great advantage that no independent solvent subsequently has to be worked up, i.e. separated from methanol, and the purity of the final product cannot be contaminated by traces of the independent solvent.
Furthermore, the solubility of the alkali metal ~-dialkylaminoethoxide therein is better than in an extraneous solvent.
2 ~
- 4 - O.Z. 4594 When the suspension of the alkali metal ~-dialkylamino-ethanol is present, the reaction with alkyl halides, for example ethyl chloride, methyl bromide and the like, is subsequently carried out, the alkyl chlorides being preferred here as higher yields can be achieved with them than with the alkyl bromides.
The alkyl halides are employed in stoichiometric amount~
or in a slight excess of up to 15 mol%. Excess unreacted alkyl halide can be returned to the alkali metal salt of (I) of the following batch by release of pressure. The reaction is carried out at temperatures from 30 to 160'C, preferably between 50 and 120C, at normal pres~ure or alternatively at pressures up to 20 bar. In this process, the alkyl halide is metered in at the reaction tempera-ture in a period of 50 to 80 minutes, partly using ametering pump against the pressure of the reaction solution. The reaction i8 slightly exothermic snd ths reaction time therefore depends on the size of the batches and on the possibility of heat dissipation. The post-reaction time is another 2 to 6 hours.
After the end of the reaction, the alkali metal halide, for example NaCl, is to be filtered off or all of the volatile fraction is to be di~tilled off from the ~alt.
~`
Distillation of the pure product follows as the last working-up step. Unfortunately, the starting material ~-dialkylaminoethanol forms with many solvents such as toluene and cyclohexane the respective azeotropes which have solvent contents of only a few per cent. ~ven from the target product, for example 1-dimethylamino-2-ethoxy-ethane, ~-dimethylaminoethanol can only be distilled off in a highly complicated distillation through columns having a theoretical number of 6tages of more than S0. It is therefore expedient to lower the dialkylaminoethanol in the crude target product as far as possible. This is possible if alkali metal alkoxide corresponding to the low content of ~-dialkylaminoethanol ~s added and thus 2~71~ ~
- S - O.Z. 4594 the dialkylamino alcohol is bound as the alkoxide ~alt in the distillation bottom. A S to lS mol% strength excess of alkali metal alkoxide is prefarably employed. In the distillation of the pure product, the simple alcohol is S therefore first distilled off as a forerun, before the target product distils over as the main fraction. This di~tillation of pure product can be carried out at normal pressure or under a ~light vacuum and does not require a highly complicated separation.
In this manner, purities of 1-alkoxydialkylamino-2-ethanes of 99.9% are achieved.
( The alkali metal salt of the dialkylaminoethanol remains in the distillation bottom in addition to some alkali metal alkoxide suspended in the target product, which i~
returned to the synthesis reactor. No losses of starting material thus result. For this reason, the yields of l-alkoxy-2-dialkylaminoethane are also very high at 95 of theory.
Example 1 (for comparison) l-Etho y-2-dimethyl~minoethane (KDE) 359 g of 30% strength sodium methoxide solution (2.0 mol) are introduced into a glass autoclave which is equipped ( with a stirrer, temperature measuring device, pressure-tight distillation section and alkyl halide metering pump and the methanol is removed by distillation up to a bottom temperature of 130C. 214 g of ~-dimethylamino-ethanol DMAE (2.4 mol) and 700 ml of cyclohexane are then added and all the methanol is removed by distillation up to a bottom temperature of 85C.
After cooling to 2SC, 22 g of ethyl bromide (2.04 mol) are to be pumped in in 1 h and the reaction i~ to be completed at 65C in 4 to S h. After cooling to 20C, NaBr i8 filtered off, washed with cyclohexane and dried:
219 g (106% of theory by quaternary ammonium salts). The filtrate is rectified in a 1 m long laboratory column.
~1 7` ~
- 6 - O.Z. ~59~
Cyclohexane initially di~til~ off, then the mRin fraction and ~ubsequently a fraction rich of dimethylaminoethan (b.p.: 95 to 98C at 500 mbar).
Main fraction: 196.7 g containing 94.1% EDE, 5.4% D~AE
Subsequent 30.3 g containing 3.3% BDB, 89.3% DMAE
fraction:
Yield: 186.1 g of EDE (79.5~ of theory) DMAE recovery:
as an azeotrope with cyclohexane, altogether 60 g of DMAE
(0.67 mol) distil off in the main and subsQquent fraction (determined from final weight and G.C. purity), which doe~ not correspond completely to the excess (35.6 g) and unreacted product.
B~ample 2 (for comparison) 1-Btho~y-2-dimethylaminoethanQ (EDE) 359 g of 30% strength by weight methanolic sodium methoxide solution (2.0 mol) are concentrated to dryness in the autoclave (as described in Example 1) and then 172 g of p-dimethylaminoethanol and, from preliminarr experiments, 800 g of c~lohe~anQ which still cont~ins 42 g of D~AB dissolved (altogother 214 g of nY~, 2.4 mol~ are introduced. All the methanol i8 di~tilled off as an azeotrope, then the autoclave i~ sealed and, at about lOO-C, 142 g of ethyl chloride (2.2 mol) are to be pumped in at a pressure of 2 to 3 bar in 1.5 h. The post-reactlon time i~ 3 h. After cooling, the NaCl is filtered off, washed and dried (110 g, 94.1% of theory).
All the filtrates are rectified through a 1 m long laboratory column in a vacuum of 500 mbar and under reflux. After removal of cyclohexane, an EDE main fraction and a smaller DMAE subsequent fraction distil.
~ain fraction: 222 g containing 94.7~ EDE, 4.9% D~AB
Subsequent lS.5 g containing 64.4% EDE, 35% DMAE
fraction:
Yield: 220.2 g of EDE (94.0% of theory).
2~7~
- 7 - O.Z. 4594 The excess of DMA~ (O.4 mol) ~ distributed in the two distillation fractions (16.3 g) and in the cyclohexane forerun.
~xample 3 (invention) 1-Ethoxy-2-dimethylaminoethane (EDE) 361 g of 29.9% strength by weight methanolic NaOCH3 (2.0 mol) are evaporated to dryness in the apparatus described above and 188 g of DMAE containing 800 g of EDE, which still contains 8 g of DMAE (together DMA~:
196 g, 2.2 mol) are introduced.
All the methanol is distilled off. At 100C, 142 g of ethyl chloride (2.2 mol) are pumped into the sealed apparatus at a pre~sure of about 1.5 bar in the course of 1.5 h. The reaction is complete after a post-reaction time of 3 h at lOO-C.
All the EDE is distilled off from the NaCl in a vacuum of 500 mbar.
(NaCl: 117 g, 100% of theory).
1106 g of distillate are obtained having a DMAE content of 2.9% (corresponding to 0.36 mol). For binding as the Na salt, 72 g of 30% strength by weight methanolic NaOCH3 solution (0.40 mol) are added and the whole mixture is distilled through a column. After removing all the Ci methanol and a small intermediate fraction, very pure EDE
distils over at 120C. The Na salt of DNAE containing some EDE remains in the distillate bottom, and is added to the following batch during the formation of Na DMAE.
Yield: 1015 g (le~s 800 g of solvent) 215 g of EDE (91.9% of theory, 95% including bottom) G.C. purity: 99.9%.
Yield after four batches with return of EDE and Na DMAE
gives 96% yield.
, S, ~ IJ J
- 8 - O.Z. 4594 ~ample 4 (.inv~ntion) I-~thoxy-2-d.imethyl.~m;.noethane (EDE~
The distillation hottom from Example 3, which contains 0.36 mol of Na salt of D~AE ancl 0.04 mol of NaOCH3, i8 treat~d with 1.96 mol ~f fresh NaOCH3 solution and the me~hanol is di~tilled off. 1.84 mol of DMAE (164 g) ar.d 800 g of ED~ are then added and the Na DMAE i8 formed with removal of all the methanol by di~tillation.
The additional reaction ~equence proceeds a~ de~cribed in Ex~mple 3.
The yield of EDE is 222 g (95% of theory) After four batches with return of EDE and Na DMAE, a yield of ~7~ and a puri-ty of 99.8% re~ults.
Example 5 (invention) 1-Ethoxy-2-diethylaminoethane (EDEE) 359 g of 30% strength by weight NaOCH3 solution t2.0 mol) are concentrated to dryness (130C) in the autoclave described in Example 1, 281 g of 2-diethylaminoethanol (DEAE, 2.4 mol) and lO00 ml of t-butyl methyl ether are introduced and all the methanol is removed by azeotropic distillation. At a temperature of 100C, 142 g of ethyl chloride (2.2 mol) are pumped in in the course of 1.5 h and the reaction is then completed in a further 3 h (pressure: 1 to 3.5 bar). After cooling, the NaCl i8 filtered off, washed with t-butyl methyl ether and dried (114 g, 97.5% of theory) The collected filtrates are distilled through a column;
EDEE containing 5% DEAE as the main fraction distils over after removal of the solvent. A small DEAE-rich fraction remains in the distillation bottom. The main fraction is treated with 1.1 times the equivalent amount of NaOCH3 solution - relative to residual DEAE - and again sub-jected to fractional distillation. After distilling off the methanol forerun, very pure EDEE distils over at 710C/40 mbar. The bottom remaining from this distilla-tion of pure product, which contains the Na salt from DEAE, is employed again for subsequent batches, in which EDEE is then used as the solvent (instead of t-butyl _ g _ o.z. 4594 methyl ether); the yields rise above 90~ on frequently repeated reuse of the distillation bottom.
Yield: 240.5 g (82.9~, relative to Na methoxide; includ-ing 95% bottom).
After returning four times, yields of 95~ and purities of over 99.5~ are obtained.
Examples 6 to 9 Example 6: 1-Propoxy-2-dimethylaminoethane (PDM~) Example 7: 1-Butoxy-2-dimethylaminoethane (BDME) Example 8: 1-Propoxy-2-diethylaminoethane (PDEE) Example 9: 1-Butoxy-2-diethylaminoethane (BDEE) In accordance with the procedure of Example 5, both ~-dimethyl- and ~-diethylaminoethanol are reacted in the solvents cyclohexane or t-butyl methyl ether with n-propyl chloride and n-butyl chloride to give the corresponding aminoalkyl ethers.
Under a pressure of 1 to 3 bar, the reaction temperatures in the autoclave are 100 to 115C.
The maximum yields and purities are only obtained after two to four batch cycles using the target product as solvent and returning the Na dialkylaminoethoxide from the distillation bottom.
- 10 - O. 8 . ~59~
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,~ a~ ~ co co ___ _ ~
~u ~ 8 u~ u~ ~ d' O ~ ~
_ __ ~ ~ U~
~J ~ ~ N N N
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_I ~ er ~ ~O' ~3 ~ ~J N ~ N
._ ~ ~ ~ ~
o o c~ o r~
-u~
The alkyl halides are employed in stoichiometric amount~
or in a slight excess of up to 15 mol%. Excess unreacted alkyl halide can be returned to the alkali metal salt of (I) of the following batch by release of pressure. The reaction is carried out at temperatures from 30 to 160'C, preferably between 50 and 120C, at normal pres~ure or alternatively at pressures up to 20 bar. In this process, the alkyl halide is metered in at the reaction tempera-ture in a period of 50 to 80 minutes, partly using ametering pump against the pressure of the reaction solution. The reaction i8 slightly exothermic snd ths reaction time therefore depends on the size of the batches and on the possibility of heat dissipation. The post-reaction time is another 2 to 6 hours.
After the end of the reaction, the alkali metal halide, for example NaCl, is to be filtered off or all of the volatile fraction is to be di~tilled off from the ~alt.
~`
Distillation of the pure product follows as the last working-up step. Unfortunately, the starting material ~-dialkylaminoethanol forms with many solvents such as toluene and cyclohexane the respective azeotropes which have solvent contents of only a few per cent. ~ven from the target product, for example 1-dimethylamino-2-ethoxy-ethane, ~-dimethylaminoethanol can only be distilled off in a highly complicated distillation through columns having a theoretical number of 6tages of more than S0. It is therefore expedient to lower the dialkylaminoethanol in the crude target product as far as possible. This is possible if alkali metal alkoxide corresponding to the low content of ~-dialkylaminoethanol ~s added and thus 2~71~ ~
- S - O.Z. 4594 the dialkylamino alcohol is bound as the alkoxide ~alt in the distillation bottom. A S to lS mol% strength excess of alkali metal alkoxide is prefarably employed. In the distillation of the pure product, the simple alcohol is S therefore first distilled off as a forerun, before the target product distils over as the main fraction. This di~tillation of pure product can be carried out at normal pressure or under a ~light vacuum and does not require a highly complicated separation.
In this manner, purities of 1-alkoxydialkylamino-2-ethanes of 99.9% are achieved.
( The alkali metal salt of the dialkylaminoethanol remains in the distillation bottom in addition to some alkali metal alkoxide suspended in the target product, which i~
returned to the synthesis reactor. No losses of starting material thus result. For this reason, the yields of l-alkoxy-2-dialkylaminoethane are also very high at 95 of theory.
Example 1 (for comparison) l-Etho y-2-dimethyl~minoethane (KDE) 359 g of 30% strength sodium methoxide solution (2.0 mol) are introduced into a glass autoclave which is equipped ( with a stirrer, temperature measuring device, pressure-tight distillation section and alkyl halide metering pump and the methanol is removed by distillation up to a bottom temperature of 130C. 214 g of ~-dimethylamino-ethanol DMAE (2.4 mol) and 700 ml of cyclohexane are then added and all the methanol is removed by distillation up to a bottom temperature of 85C.
After cooling to 2SC, 22 g of ethyl bromide (2.04 mol) are to be pumped in in 1 h and the reaction i~ to be completed at 65C in 4 to S h. After cooling to 20C, NaBr i8 filtered off, washed with cyclohexane and dried:
219 g (106% of theory by quaternary ammonium salts). The filtrate is rectified in a 1 m long laboratory column.
~1 7` ~
- 6 - O.Z. ~59~
Cyclohexane initially di~til~ off, then the mRin fraction and ~ubsequently a fraction rich of dimethylaminoethan (b.p.: 95 to 98C at 500 mbar).
Main fraction: 196.7 g containing 94.1% EDE, 5.4% D~AE
Subsequent 30.3 g containing 3.3% BDB, 89.3% DMAE
fraction:
Yield: 186.1 g of EDE (79.5~ of theory) DMAE recovery:
as an azeotrope with cyclohexane, altogether 60 g of DMAE
(0.67 mol) distil off in the main and subsQquent fraction (determined from final weight and G.C. purity), which doe~ not correspond completely to the excess (35.6 g) and unreacted product.
B~ample 2 (for comparison) 1-Btho~y-2-dimethylaminoethanQ (EDE) 359 g of 30% strength by weight methanolic sodium methoxide solution (2.0 mol) are concentrated to dryness in the autoclave (as described in Example 1) and then 172 g of p-dimethylaminoethanol and, from preliminarr experiments, 800 g of c~lohe~anQ which still cont~ins 42 g of D~AB dissolved (altogother 214 g of nY~, 2.4 mol~ are introduced. All the methanol i8 di~tilled off as an azeotrope, then the autoclave i~ sealed and, at about lOO-C, 142 g of ethyl chloride (2.2 mol) are to be pumped in at a pressure of 2 to 3 bar in 1.5 h. The post-reactlon time i~ 3 h. After cooling, the NaCl is filtered off, washed and dried (110 g, 94.1% of theory).
All the filtrates are rectified through a 1 m long laboratory column in a vacuum of 500 mbar and under reflux. After removal of cyclohexane, an EDE main fraction and a smaller DMAE subsequent fraction distil.
~ain fraction: 222 g containing 94.7~ EDE, 4.9% D~AB
Subsequent lS.5 g containing 64.4% EDE, 35% DMAE
fraction:
Yield: 220.2 g of EDE (94.0% of theory).
2~7~
- 7 - O.Z. 4594 The excess of DMA~ (O.4 mol) ~ distributed in the two distillation fractions (16.3 g) and in the cyclohexane forerun.
~xample 3 (invention) 1-Ethoxy-2-dimethylaminoethane (EDE) 361 g of 29.9% strength by weight methanolic NaOCH3 (2.0 mol) are evaporated to dryness in the apparatus described above and 188 g of DMAE containing 800 g of EDE, which still contains 8 g of DMAE (together DMA~:
196 g, 2.2 mol) are introduced.
All the methanol is distilled off. At 100C, 142 g of ethyl chloride (2.2 mol) are pumped into the sealed apparatus at a pre~sure of about 1.5 bar in the course of 1.5 h. The reaction is complete after a post-reaction time of 3 h at lOO-C.
All the EDE is distilled off from the NaCl in a vacuum of 500 mbar.
(NaCl: 117 g, 100% of theory).
1106 g of distillate are obtained having a DMAE content of 2.9% (corresponding to 0.36 mol). For binding as the Na salt, 72 g of 30% strength by weight methanolic NaOCH3 solution (0.40 mol) are added and the whole mixture is distilled through a column. After removing all the Ci methanol and a small intermediate fraction, very pure EDE
distils over at 120C. The Na salt of DNAE containing some EDE remains in the distillate bottom, and is added to the following batch during the formation of Na DMAE.
Yield: 1015 g (le~s 800 g of solvent) 215 g of EDE (91.9% of theory, 95% including bottom) G.C. purity: 99.9%.
Yield after four batches with return of EDE and Na DMAE
gives 96% yield.
, S, ~ IJ J
- 8 - O.Z. 4594 ~ample 4 (.inv~ntion) I-~thoxy-2-d.imethyl.~m;.noethane (EDE~
The distillation hottom from Example 3, which contains 0.36 mol of Na salt of D~AE ancl 0.04 mol of NaOCH3, i8 treat~d with 1.96 mol ~f fresh NaOCH3 solution and the me~hanol is di~tilled off. 1.84 mol of DMAE (164 g) ar.d 800 g of ED~ are then added and the Na DMAE i8 formed with removal of all the methanol by di~tillation.
The additional reaction ~equence proceeds a~ de~cribed in Ex~mple 3.
The yield of EDE is 222 g (95% of theory) After four batches with return of EDE and Na DMAE, a yield of ~7~ and a puri-ty of 99.8% re~ults.
Example 5 (invention) 1-Ethoxy-2-diethylaminoethane (EDEE) 359 g of 30% strength by weight NaOCH3 solution t2.0 mol) are concentrated to dryness (130C) in the autoclave described in Example 1, 281 g of 2-diethylaminoethanol (DEAE, 2.4 mol) and lO00 ml of t-butyl methyl ether are introduced and all the methanol is removed by azeotropic distillation. At a temperature of 100C, 142 g of ethyl chloride (2.2 mol) are pumped in in the course of 1.5 h and the reaction is then completed in a further 3 h (pressure: 1 to 3.5 bar). After cooling, the NaCl i8 filtered off, washed with t-butyl methyl ether and dried (114 g, 97.5% of theory) The collected filtrates are distilled through a column;
EDEE containing 5% DEAE as the main fraction distils over after removal of the solvent. A small DEAE-rich fraction remains in the distillation bottom. The main fraction is treated with 1.1 times the equivalent amount of NaOCH3 solution - relative to residual DEAE - and again sub-jected to fractional distillation. After distilling off the methanol forerun, very pure EDEE distils over at 710C/40 mbar. The bottom remaining from this distilla-tion of pure product, which contains the Na salt from DEAE, is employed again for subsequent batches, in which EDEE is then used as the solvent (instead of t-butyl _ g _ o.z. 4594 methyl ether); the yields rise above 90~ on frequently repeated reuse of the distillation bottom.
Yield: 240.5 g (82.9~, relative to Na methoxide; includ-ing 95% bottom).
After returning four times, yields of 95~ and purities of over 99.5~ are obtained.
Examples 6 to 9 Example 6: 1-Propoxy-2-dimethylaminoethane (PDM~) Example 7: 1-Butoxy-2-dimethylaminoethane (BDME) Example 8: 1-Propoxy-2-diethylaminoethane (PDEE) Example 9: 1-Butoxy-2-diethylaminoethane (BDEE) In accordance with the procedure of Example 5, both ~-dimethyl- and ~-diethylaminoethanol are reacted in the solvents cyclohexane or t-butyl methyl ether with n-propyl chloride and n-butyl chloride to give the corresponding aminoalkyl ethers.
Under a pressure of 1 to 3 bar, the reaction temperatures in the autoclave are 100 to 115C.
The maximum yields and purities are only obtained after two to four batch cycles using the target product as solvent and returning the Na dialkylaminoethoxide from the distillation bottom.
- 10 - O. 8 . ~59~
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,~ a~ ~ co co ___ _ ~
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_ __ ~ ~ U~
~J ~ ~ N N N
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_I ~ er ~ ~O' ~3 ~ ~J N ~ N
._ ~ ~ ~ ~
o o c~ o r~
-u~
Claims (18)
1. A process for the preparation of a 1-alkoxy-2-dialkyl-aminoethane of the formula (III):
(III) wherein R1 and R2 represent a C1-C10-alkyl, which process comprises:
a) reacting .beta.-dialkylaminoethanol of the formula (I):
(I) wherein R1 is as defined above, with an alkali metal alkoxide of a simple alcohol, with total removal of the simple alcohol, b) reacting the alkali metal .beta.-dialkylaminoethoxide so obtained with an alkyl halide of the formula (II):
R2 - X (II) wherein R2 is as defined above and X is Cl, Br or I, and c) recovering the 1-alkoxy-2-dialkylaminoethane so obtained.
(III) wherein R1 and R2 represent a C1-C10-alkyl, which process comprises:
a) reacting .beta.-dialkylaminoethanol of the formula (I):
(I) wherein R1 is as defined above, with an alkali metal alkoxide of a simple alcohol, with total removal of the simple alcohol, b) reacting the alkali metal .beta.-dialkylaminoethoxide so obtained with an alkyl halide of the formula (II):
R2 - X (II) wherein R2 is as defined above and X is Cl, Br or I, and c) recovering the 1-alkoxy-2-dialkylaminoethane so obtained.
2. A process according to claim 1, wherein the alkali metal is sodium or potassium.
3. A process according to claim 1, wherein the simple alcohol is a short-chain alcohol having 1 to 3 carbon atoms.
4. A process according to claim 3, wherein the short-chain alcohol is methanol.
5. A process according to claim 1, 2, 3 or 4, wherein in step a) an excess of from about 0.1 to about 30 mol%, relative to the alkali metal alkoxide, of the .beta.-dialkylamino-ethanol is used.
6. A process according to claim 1, wherein the excess is from about 5 to about 20 mol%.
7. A process according to claim 1, 2, 3, 4 or 6, wherein the total removal of the simple alcohol is carried out by distillation with an inert solvent.
8. A process according to claim 7, wherein the inert solvent is an aliphatic or aromatic hydrocarbon.
9. A process according to claim 1, 2, 3, 4 or 6, wherein the total removal of the simple alcohol is carried out by distillation with the 1-alkoxy-2-dialkylaminoethane to be prepared.
10. A process according to claim 1, 2, 3, 4, 6 or 8, wherein the reaction of step b) is carried out at a temperature of from about 30 to about 160°C.
11. A process according to claim 10, wherein the reaction of step b) is carried out at a temperature of from about 50 to about 120°C.
12. A process according to claim 1, 2, 3, 4, 6, 8 or 10, wherein the reaction of step b) is carried out at atmospheric pressure.
13. A process according to claim 1, 2, 3, 4, 6, 8 or 10, wherein the reaction of step b) is carried out at a pressure of up to 20 bar.
14. A process according to claim 1, 2, 3, 4, 6, 8 or 10, wherein the recovery of the 1-alkoxy-2-dialkylaminoethane is carried out by distillation.
15. A process according to claim 14, wherein the distillation is carried out in the presence of an alkali metal alkoxide.
16. A process according to claim 15, wherein the alkali metal alkoxide is sodium or potassium alkoxide.
17. A process according to claim 15 or 16, wherein the amount of the alkali metal alkoxide is at least stoichio-metrically equivalent to the residual .beta.-dialkylaminoethanol.
18. A process according to claim 17, wherein an excess of up to 15 mol% of the alkali metal alkoxide is used.
20. A process according to claim 1, 2, 3, 4, 6, 8, 10, 15, 16 or 18, wherein R1 is a C1-C3-alkyl.
21. A process according to claim 1, 2, 3, 4, 6, 8, 10, 15, 16 or 18, wherein R2 is a C1-C3-alkyl.
22. A process according to claim 1, 2, 3, 4, 6, 8, 10, 15, 16 or 18, wherein X is C1.
20. A process according to claim 1, 2, 3, 4, 6, 8, 10, 15, 16 or 18, wherein R1 is a C1-C3-alkyl.
21. A process according to claim 1, 2, 3, 4, 6, 8, 10, 15, 16 or 18, wherein R2 is a C1-C3-alkyl.
22. A process according to claim 1, 2, 3, 4, 6, 8, 10, 15, 16 or 18, wherein X is C1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19914119576 DE4119576A1 (en) | 1991-06-14 | 1991-06-14 | PROCESS FOR PREPARING 1-ALKOXY-2-DIALKYLAMINO-ETHANESE |
| DEP4119576.0 | 1991-06-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2071102A1 true CA2071102A1 (en) | 1992-12-15 |
Family
ID=6433900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2071102 Abandoned CA2071102A1 (en) | 1991-06-14 | 1992-06-12 | Process for the preparation of 1-alkoxy-2-dialkylaminoethanes |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0518013A3 (en) |
| JP (1) | JPH05155826A (en) |
| CA (1) | CA2071102A1 (en) |
| DE (1) | DE4119576A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5710099A (en) * | 1996-02-27 | 1998-01-20 | The United States Of America As Represented By The Secretary Of Agriculture | Bioactive compounds |
| DE10252413A1 (en) * | 2002-11-12 | 2004-05-27 | Degussa Ag | Process for the preparation of solutions of alkali metal salts of functionalized alcohols |
| DE10342647A1 (en) * | 2003-09-16 | 2005-04-07 | Degussa Ag | Process for the preparation of 2- (N, N-dialkylamino) ethoxy compounds |
| DE10344447A1 (en) * | 2003-09-25 | 2005-05-12 | Degussa | Producing O-alkylated amino alcohols, e.g. useful as intermediates for bioactive agents, comprises reacting an amino alcohol with an alkali metal alkoxide and reacting the resulting salt with an alkyl halide |
| JP6108197B2 (en) * | 2012-07-02 | 2017-04-05 | 日油株式会社 | Method for producing tertiary amino group-containing lipid |
| CN111100019B (en) * | 2020-01-08 | 2023-04-07 | 浙江工业大学 | N, N-di-N-propyl-2-propoxyethylamine and preparation method and application thereof |
| CN115611762B (en) * | 2022-10-17 | 2023-12-29 | 安徽瑞辰植保工程有限公司 | Continuous production process of herbicide |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4588843A (en) * | 1984-04-26 | 1986-05-13 | Ethyl Corporation | Synthesis of (alkoxyalkyl) amines |
-
1991
- 1991-06-14 DE DE19914119576 patent/DE4119576A1/en not_active Withdrawn
-
1992
- 1992-04-02 EP EP19920105667 patent/EP0518013A3/en not_active Withdrawn
- 1992-06-11 JP JP15177592A patent/JPH05155826A/en active Pending
- 1992-06-12 CA CA 2071102 patent/CA2071102A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0518013A3 (en) | 1993-04-28 |
| JPH05155826A (en) | 1993-06-22 |
| DE4119576A1 (en) | 1992-12-17 |
| EP0518013A2 (en) | 1992-12-16 |
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