CA1170661A - Liquid phase preparation of 2-substituted-2- oxazolines with organic zinc salt catalysts - Google Patents
Liquid phase preparation of 2-substituted-2- oxazolines with organic zinc salt catalystsInfo
- Publication number
- CA1170661A CA1170661A CA000413167A CA413167A CA1170661A CA 1170661 A CA1170661 A CA 1170661A CA 000413167 A CA000413167 A CA 000413167A CA 413167 A CA413167 A CA 413167A CA 1170661 A CA1170661 A CA 1170661A
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- CA
- Canada
- Prior art keywords
- substituted
- carboxamide
- oxazoline
- zinc salt
- oxazolines
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Catalysts (AREA)
Abstract
ABSTRACT
2-Substituted-2-oxazolines are prepared by con-tacting N-(2-hydroxyalkyl)carboxamides with a catalytic amount of an organic zinc salt at an elevated temperature.
18,266E-F. -9-
2-Substituted-2-oxazolines are prepared by con-tacting N-(2-hydroxyalkyl)carboxamides with a catalytic amount of an organic zinc salt at an elevated temperature.
18,266E-F. -9-
Description
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LIQUID PHASE PREPARATION
WITH ORGANIC ZINC SALT CATALYSTS
LIQUID PHASE PREPARATION
WITH ORGANIC ZINC SALT CATALYSTS
2-Substituted-2-oxazolines form a known class of compounds having many members and many utilities. The chem-istry of such oxazolines has been summarized, for example, by Wiley et al., Chemical Reviews, Vol. 44, 447 (1949), by Seeliger et al., Angew. Chem. International Edition, Vol. 5, No. 10, 875 (1966), and by Frump, Chemical Reviews, Vol. 71, No. 5, 483 (1971).
One of the prior art processes for preparing 2-substituted-2-oxazolines is the cyclodehydration of N-(b-hydroxyalkyl)carboxamides. This cyclodehydration occurs in vapor phase over alumina (U.S. Patent 3,562,263 and Frump, as mentioned above, page 485) and in liquid phase over certain salts of manganese, cobalt, rare earth metals, molybdenum and tungsten (U.S. Patents 3,681,329 and
One of the prior art processes for preparing 2-substituted-2-oxazolines is the cyclodehydration of N-(b-hydroxyalkyl)carboxamides. This cyclodehydration occurs in vapor phase over alumina (U.S. Patent 3,562,263 and Frump, as mentioned above, page 485) and in liquid phase over certain salts of manganese, cobalt, rare earth metals, molybdenum and tungsten (U.S. Patents 3,681,329 and
3,681,333). The latter two patents indicate that the cyclodehydration reaction is brought about by heating the hydroxyamide and catalyst together in a distillation apparatus from which the oxazoline product distills from the reaction mixture as it is formed along with the by-product water.
,~
18,266E-F 1~
In another process, 2-substituted-2-oxazolines are prepared by heating N-(2-hydroxyalkyl)carboxamides in the presence of certain inorganic iron salts (European Patent Publication 0033752, published August 19, 1981, The Dow Chemical Company). However, this process does not result in as high yields as does the invention described in this application.
The present invention is a cyclodehydration process for making a 2-substituted-2-oxazoline characterized by reacting in the liquid phase an N-(2-hydroxyalkyl)-carboxamide having the formula R-C-~I-CH2CH20H
where R is alkyl of l to 17 carbon atoms or phenyl, or a carboxylic acid/amine salt precursor of said carboxamide with a catalytic amount of an organic zinc salt.
The temperature/pressure relationship is normally adjusted such that the oxazoline and water codistill from the reaction mixture essentially as fast as they are formed.
The N-(b-hydroxyalkyl)carboxamides used in the instant process have the formula o I. R-C-NH-CH2-CH2-OH
wherein R is alkyl of 1 to 7 carbon atoms, or phenyl, or a carboxylic acid/amine salt precursor of said carboxamide. Such carboxamides are typically prepared 18,266E-F -2-by reacting a carboxylic acid or a lower alkyl ester of the carboxylic acid with an ethanolamine of the formula The carboxylic acid/amine salt which is formed initially in these reactions can be used in the instant process in place of the carboxamide. When such carboxylic acid/amine salts are used, the carboxamide is generated ln situ. R in formula I is preferably methyl, ethyl or phenyl and more preferably methyl or ethyl. Examples of suitable N-(b-hydroxyalkyl)-carboxamides include compounds of formula I having the following values for R: CH3, C2H5, C3H7, C7H15, CgH19, CllH23~ C17H35~ C6H5~ C6H4CH3~ C6HsCH2, CH3(CH2~7CH=CH(CH2)7 and cyclohexyl.
The catalysts in the instant cyclodehydration reaction are organic zinc salts which are soluble in the carboxamide reactant or liquid reaction medium. The term "soluble" is not meant to imply that the zinc salt is solu-ble or miscible in all proportions with the carboxamide or liquid reaction medium, but instead has at least a minimum solubility (e.g., at least about 100 parts per million or more) at reaction temperature. Such zinc salts are used in the process in catalytic amounts. Normally, the zinc salts are charged in amounts of from 0.005 to 0.4 mole of zinc salt per mole of carboxamide reactant, but more or less of the zinc salts can be used, if desired. Car-boxylic acid salts of zinc having the formula (RC00 )2Zn wherein R is a Cl-C20 aliphatic or alicyclic radical or an inertly-substituted C1-C20 aliphatic or alicyclic carboxylic acid radical may be used as catalysts in the invention.
18,266E-F -3-fi Suitable carboxylic acid zinc salts include, for example, zinc acetate, zinc formate, zinc propionate, zinc stearate and zinc neodecanoate. Zinc acetate is the current pre-ferred catalyst.
The instant cyclodehydration reaction may be con-ducted neat or in solution with a suitable inert solvent.
By "inert" is meant inert in the process. Suitable such inert solvents include, for examPle, chlorinated hydro-carbon solvents, aromatic hydrocarbons, cycloaliphatic hydro~
carbons and aliphatic hydrocarbons. It is preferred however, to conduct the reaction neat.
The reaction temperature must, obviously, be suf-ficient to promote the cyclodehydration reaction and is nor~
mally selected in the range of from about 140C to about 280C. Preferred reaction rates have beèn observed at tem-peratures of from about 160C to about 250C. The instant cyclodehydration reaction is also preferably conducted under reduced pressure. This facilitates product recovery in that frequently a reaction temperature may be chosen which is above the boiling point of the 2-substituted-2-oxazoline product and below the boiling point of the N-(b-hydroxy-alkyl)carboxamide. In this manner, the 2-substituted-2--oxazoline can be removed from the reaction mixture as a volatile gas essentially as fast as it is formed. This is very desirable since the instant cyclodehydration reaction is a reversible process and by removing the products, the reaction is forced to completion by substantially reducing the reverse reaction. Water normally codistills with the 2-substituted-2-oxazoline product.
The instant process may be conducted in a batch process or by a continuous process. In the preferred con-tinuous process the N-(b-hydroxyalkyl~carboxamide reactant 18,266E-F -4-is metered into the reaction vessel at essentially the same rate as the 2-substituted-2-oxazoline and water are removed.
The following examples further illustrate the invention.
Example 1 - Preparation of 2-Ethyl-2-Oxazoline Over Zinc Acetate Dihydrate Zinc acetate dihydrate (10.0 g; 0.045 mole) and 95.4 percent pure N-(b-hydroxyethyl)propionamide (20.0 g;
0.162 mole) were charged to a reaction vessel e~uipped with a stirring means, a metering pump, and a 5-plate distillation column with a take-off head. The pressure over the reaction mixture was adjusted to 50 mm Hg and the reaction mixture heated to 200C. The reaction mixture was held at 200C and 95.4 percent pure N-(b-hydroxyethyl)propionamide (290 g; 2.35 mole) was pumped in at approximately 0.9 g/min to the system. As the propionamide was added to the reac-tion mixture, a water-white distillate was collected over-head through the distillation apparatus at a head temperature of 40C 45C. After the addition of the propionamide was complete, the pot was heated to 220C to drive off the last amounts of 2-ethyl-2-oxazoline. The overhead distillate temperatuxe reached a maximum of 41C during this post--heating step. A total of 294.8 g of water-white distillate was thus obtained overhead leaving 21.7 g of a tan, wet paste remaining in the pot. Analysis of the distillate overheads by gas chromatography using an internal standard and a Karl Fischer water titration showed the material to be 2-ethyl-2-oxazoline, water and very minor amounts of 18,266E-F -5-unreacted propionamide and 2-methyl-2-oxazoline. The impur-ities in the propionamide reactant were: water (approxi-mately 1 percent); monoethanolamine (approximately 2-3 per-cent); and the amidoester of propionic acid and monoethanol-amine (approximately 1 percent).
The oxazoline was produced in 96.2 percent yield, based on the pure N-(b-hydroxyethyl)propionamide charged to the system. The amount of water produced according to analy-sis was 93.0 percent of theory. The 2-ethyl-2-oxazoline can be easily separated from the mixture by selective extraction using diethylbenzene followed by distillation.
ExamPle 2 In another experiment, 2-ethyl-2-oxazoline was prepared in 82 percent yield by warming a propionic acid/-ethanolamine salt in the presence of approximately 2 molepercent zinc acetate dihydrate at a temperature of 200C/50 mm Hg. This was a batch experiment in which the acid/amine salt and catalyst were initially charged and warmed to the indicated reaction temperature. There was a pause in the rise in temperature during which the acid/amine salt was converted to the amide. Otherwise, this reaction proceeded the same as Example 1 above. The product was similarly recovered as an overhead distillate with water.
Other catalysts and carboxamide reactants as set forth above could be similarly used to produce the 2-substi-tuted-2-oxazolines.
18,266E-F -6-
,~
18,266E-F 1~
In another process, 2-substituted-2-oxazolines are prepared by heating N-(2-hydroxyalkyl)carboxamides in the presence of certain inorganic iron salts (European Patent Publication 0033752, published August 19, 1981, The Dow Chemical Company). However, this process does not result in as high yields as does the invention described in this application.
The present invention is a cyclodehydration process for making a 2-substituted-2-oxazoline characterized by reacting in the liquid phase an N-(2-hydroxyalkyl)-carboxamide having the formula R-C-~I-CH2CH20H
where R is alkyl of l to 17 carbon atoms or phenyl, or a carboxylic acid/amine salt precursor of said carboxamide with a catalytic amount of an organic zinc salt.
The temperature/pressure relationship is normally adjusted such that the oxazoline and water codistill from the reaction mixture essentially as fast as they are formed.
The N-(b-hydroxyalkyl)carboxamides used in the instant process have the formula o I. R-C-NH-CH2-CH2-OH
wherein R is alkyl of 1 to 7 carbon atoms, or phenyl, or a carboxylic acid/amine salt precursor of said carboxamide. Such carboxamides are typically prepared 18,266E-F -2-by reacting a carboxylic acid or a lower alkyl ester of the carboxylic acid with an ethanolamine of the formula The carboxylic acid/amine salt which is formed initially in these reactions can be used in the instant process in place of the carboxamide. When such carboxylic acid/amine salts are used, the carboxamide is generated ln situ. R in formula I is preferably methyl, ethyl or phenyl and more preferably methyl or ethyl. Examples of suitable N-(b-hydroxyalkyl)-carboxamides include compounds of formula I having the following values for R: CH3, C2H5, C3H7, C7H15, CgH19, CllH23~ C17H35~ C6H5~ C6H4CH3~ C6HsCH2, CH3(CH2~7CH=CH(CH2)7 and cyclohexyl.
The catalysts in the instant cyclodehydration reaction are organic zinc salts which are soluble in the carboxamide reactant or liquid reaction medium. The term "soluble" is not meant to imply that the zinc salt is solu-ble or miscible in all proportions with the carboxamide or liquid reaction medium, but instead has at least a minimum solubility (e.g., at least about 100 parts per million or more) at reaction temperature. Such zinc salts are used in the process in catalytic amounts. Normally, the zinc salts are charged in amounts of from 0.005 to 0.4 mole of zinc salt per mole of carboxamide reactant, but more or less of the zinc salts can be used, if desired. Car-boxylic acid salts of zinc having the formula (RC00 )2Zn wherein R is a Cl-C20 aliphatic or alicyclic radical or an inertly-substituted C1-C20 aliphatic or alicyclic carboxylic acid radical may be used as catalysts in the invention.
18,266E-F -3-fi Suitable carboxylic acid zinc salts include, for example, zinc acetate, zinc formate, zinc propionate, zinc stearate and zinc neodecanoate. Zinc acetate is the current pre-ferred catalyst.
The instant cyclodehydration reaction may be con-ducted neat or in solution with a suitable inert solvent.
By "inert" is meant inert in the process. Suitable such inert solvents include, for examPle, chlorinated hydro-carbon solvents, aromatic hydrocarbons, cycloaliphatic hydro~
carbons and aliphatic hydrocarbons. It is preferred however, to conduct the reaction neat.
The reaction temperature must, obviously, be suf-ficient to promote the cyclodehydration reaction and is nor~
mally selected in the range of from about 140C to about 280C. Preferred reaction rates have beèn observed at tem-peratures of from about 160C to about 250C. The instant cyclodehydration reaction is also preferably conducted under reduced pressure. This facilitates product recovery in that frequently a reaction temperature may be chosen which is above the boiling point of the 2-substituted-2-oxazoline product and below the boiling point of the N-(b-hydroxy-alkyl)carboxamide. In this manner, the 2-substituted-2--oxazoline can be removed from the reaction mixture as a volatile gas essentially as fast as it is formed. This is very desirable since the instant cyclodehydration reaction is a reversible process and by removing the products, the reaction is forced to completion by substantially reducing the reverse reaction. Water normally codistills with the 2-substituted-2-oxazoline product.
The instant process may be conducted in a batch process or by a continuous process. In the preferred con-tinuous process the N-(b-hydroxyalkyl~carboxamide reactant 18,266E-F -4-is metered into the reaction vessel at essentially the same rate as the 2-substituted-2-oxazoline and water are removed.
The following examples further illustrate the invention.
Example 1 - Preparation of 2-Ethyl-2-Oxazoline Over Zinc Acetate Dihydrate Zinc acetate dihydrate (10.0 g; 0.045 mole) and 95.4 percent pure N-(b-hydroxyethyl)propionamide (20.0 g;
0.162 mole) were charged to a reaction vessel e~uipped with a stirring means, a metering pump, and a 5-plate distillation column with a take-off head. The pressure over the reaction mixture was adjusted to 50 mm Hg and the reaction mixture heated to 200C. The reaction mixture was held at 200C and 95.4 percent pure N-(b-hydroxyethyl)propionamide (290 g; 2.35 mole) was pumped in at approximately 0.9 g/min to the system. As the propionamide was added to the reac-tion mixture, a water-white distillate was collected over-head through the distillation apparatus at a head temperature of 40C 45C. After the addition of the propionamide was complete, the pot was heated to 220C to drive off the last amounts of 2-ethyl-2-oxazoline. The overhead distillate temperatuxe reached a maximum of 41C during this post--heating step. A total of 294.8 g of water-white distillate was thus obtained overhead leaving 21.7 g of a tan, wet paste remaining in the pot. Analysis of the distillate overheads by gas chromatography using an internal standard and a Karl Fischer water titration showed the material to be 2-ethyl-2-oxazoline, water and very minor amounts of 18,266E-F -5-unreacted propionamide and 2-methyl-2-oxazoline. The impur-ities in the propionamide reactant were: water (approxi-mately 1 percent); monoethanolamine (approximately 2-3 per-cent); and the amidoester of propionic acid and monoethanol-amine (approximately 1 percent).
The oxazoline was produced in 96.2 percent yield, based on the pure N-(b-hydroxyethyl)propionamide charged to the system. The amount of water produced according to analy-sis was 93.0 percent of theory. The 2-ethyl-2-oxazoline can be easily separated from the mixture by selective extraction using diethylbenzene followed by distillation.
ExamPle 2 In another experiment, 2-ethyl-2-oxazoline was prepared in 82 percent yield by warming a propionic acid/-ethanolamine salt in the presence of approximately 2 molepercent zinc acetate dihydrate at a temperature of 200C/50 mm Hg. This was a batch experiment in which the acid/amine salt and catalyst were initially charged and warmed to the indicated reaction temperature. There was a pause in the rise in temperature during which the acid/amine salt was converted to the amide. Otherwise, this reaction proceeded the same as Example 1 above. The product was similarly recovered as an overhead distillate with water.
Other catalysts and carboxamide reactants as set forth above could be similarly used to produce the 2-substi-tuted-2-oxazolines.
18,266E-F -6-
Claims (6)
1. A cyclodehydration process for making a 2-substituted-2-oxazoline characterized by reacting in the liquid phase an N-(2-hydroxyalkyl)carboxamide having the formula R-?-NH-CH2CH2OH
where R is alkyl of 1 to 17 carbon atoms or phenyl, or a carboxylic acid/amine salt precursor of said carboxamide with a catalytic amount of an organic zinc salt.
where R is alkyl of 1 to 17 carbon atoms or phenyl, or a carboxylic acid/amine salt precursor of said carboxamide with a catalytic amount of an organic zinc salt.
2. The process of Claim l wherein R is methyl, ethyl or phenyl.
3. The process of Claim 1 wherein R is methyl or ethyl.
4. The process of Claim 1 wherein said catalyst is charged in amounts of from 0.005 to 0.4 mole of organic zinc salt per mole of carboxamide reactant.
5. The process of Claim 1 wherein said catalyst i6 zinc acqtats or zinc neodecanoate.
18,266E-F -7-
18,266E-F -7-
6. The process of Claim 1 wherein the process is conducted under conditions of temperature and pressure such that the 2-substituted-2-oxazoline product is removed from the reaction mixture as a volatile gas essentially as it is formed.
18,266E-F -8-
18,266E-F -8-
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000413167A CA1170661A (en) | 1982-10-08 | 1982-10-08 | Liquid phase preparation of 2-substituted-2- oxazolines with organic zinc salt catalysts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000413167A CA1170661A (en) | 1982-10-08 | 1982-10-08 | Liquid phase preparation of 2-substituted-2- oxazolines with organic zinc salt catalysts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1170661A true CA1170661A (en) | 1984-07-10 |
Family
ID=4123748
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000413167A Expired CA1170661A (en) | 1982-10-08 | 1982-10-08 | Liquid phase preparation of 2-substituted-2- oxazolines with organic zinc salt catalysts |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1170661A (en) |
-
1982
- 1982-10-08 CA CA000413167A patent/CA1170661A/en not_active Expired
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