CA1303040C - N,n'-1,3-propandiylbis(2,2-dimethyl propanamide) and a process for preparing 2-alkylpyrimidines - Google Patents
N,n'-1,3-propandiylbis(2,2-dimethyl propanamide) and a process for preparing 2-alkylpyrimidinesInfo
- Publication number
- CA1303040C CA1303040C CA000579779A CA579779A CA1303040C CA 1303040 C CA1303040 C CA 1303040C CA 000579779 A CA000579779 A CA 000579779A CA 579779 A CA579779 A CA 579779A CA 1303040 C CA1303040 C CA 1303040C
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- Prior art keywords
- propandiylbis
- alkylpyrimidines
- reaction
- diaminopropane
- preparing
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Abstract
ABSTRACT OF THE DISCLOSURE
The invention relates to a process for making 2-alkyl-pyrimidines which comprises dehydrogenating a 2-alkyltetrahydro-pyrimidine in a vapor phase reactor in the absence of oxygen and in which no water is added over a supported noble metal catalyst and the compound N,N'-1,3-propandiylbis(2,2-dimethylpropanamide). The process provides a preparation of 2-alkylpyrimidines in high yields and purity in a simple one step reaction.
The invention relates to a process for making 2-alkyl-pyrimidines which comprises dehydrogenating a 2-alkyltetrahydro-pyrimidine in a vapor phase reactor in the absence of oxygen and in which no water is added over a supported noble metal catalyst and the compound N,N'-1,3-propandiylbis(2,2-dimethylpropanamide). The process provides a preparation of 2-alkylpyrimidines in high yields and purity in a simple one step reaction.
Description
~3t~30~0 - l - 73776-5D
This divisional application is divided out of parent application serial no. 422,862 filed on March 4, 1983. The invention of this divisional application relates to a process for preparing 2-alkylpyrimidines. A further divisional application relates to the compound N,N'-1,3-propandiylbis(2,2-dimethyl-propanamide).
The invention of the parent application relates to 3-aminopropylpivalamide and a method of making it.
The preparation of tetrahydropyrimidines is discussed in "The Pyrimldines", Interscience (1962), page 445 ff. The preferred reaction involved refluxing 1,3-diaminopropane or a derivative with an alkyl ester of an organic acid, e.g., ethyl acetate or ethyl benzoate. However, when methyl pivalate was tried in this reaction, hydrolysis occurred and the resulting product was a complex mixture.
The tetrahydropyrimidines and particularly 2-t-butyl-tetrahydropyrimidine, are advantageously employed as precursors in the preparation of 0-alkyl-O[pyrimidine(5)yl]-(thiono)(thiol)-phosphoric(phosphonic)-acid esters or ester amides having exceptional insecticidal activity by the processes disclosed in, for example, United States Patent 4,127,652.
It has now been found that 3-aminopropylpivalamide can be prepared in high yields by contacting pivalic acid with 1,3-diaminopropane at temperatures above the boiling point of the 1,3-diaminopropane.
-` 13~304~
Removal of the unreacted 1,3-diaminopropane by distil-lation and dilution of the reaction mixture with a suitable solvent followed by refluxing provides 2-t-butyl-1,4,5,6-tetrahydropyrimidine in high yields.
The 3-aminopropylpivalamide prepared in this reaction is a novel compound as is N,N'-1,3-propan-diylbis(2,2-dimethylpropanamide) which is formed as a by-product. The 3-aminopropylpivalamide is advanta-geously employed to make 2-t-butyltetrahydropyrimidine which is an intermediate in the preparation of compounds having exceptional insecticidal activity.
The 3-aminopropylpivalamide is prepared by reacting pivalic acid with an excess of 1,3-diamino-propane at a temperature of 110 to 240C, preferably at 200 to 225C, for 3 to 12 hours. After removal of the unreacted 1,3-diaminopropane by distillation, the residue may be diluted with a suitable solvent and the resulting mixture refluxed, with or without pressure, at temperatures of 110 to 240C, preferably 170 to 190C, to provide 2-t-butyl-1,4,5,6-tetrahydropyrimidine.
Suitable solvents include those inert sol-vents which form azeotropes, thereby being useful to remove water from the reacting system, and have a boiling point of 110 to 240C at atmospheric condi-tions, or other inert s~lvents which will boil at 110to 240C under suitable pressure. Advantageously, - the solvent is toluene, o-xylene or diethylbenzene, although chlorinated benzenes such as monochlorobenzene and o-dichlorobenzene may be employed if desired.
29,060B-F -2-- 13~3Q~O
A 3 to 10 mole excess of 1,3-diaminopropane is usually employed, although larger molar excesses may be used, if desired. If less than a 3 molar excess is utilized, yields tend to be somewhat lower.
It has further been found that 2-t-butyl-pyrimidine, and other 2-alkylpyrimidines, can be prepared in high yields and purity in a simple one step reaction which comprises the dehydrogenation of a 2-alkyltetrahydropyrimidine under condltions which do not generate water and in which no water is added over a supported noble metal catalyst.
This reaction may be carried out neat, i.e., without employing a solvent, although an inert solvent such as, for example, pyridine may be advantageously employed.
The preferred catalysts are platinum and pal-ladium which are supported on, for example, silica gel, charcoal, activated carbon, magnesia or, pref~rably, alumina.
The reaction temperature is in the range of 250 to 450C, preferably 300 to 400C. Advantageously, the desired tetrahydropyrimidine, with or without sol-vent, is passed through a packed column containing the supported noble metal catalyst heated to the desired temperature. Feed rates to the vapor phase reactor, e.g., a 1" x 20" (2.5 x 51 cm) column containing 50 g of catalyst, are 20 to 150 ml/hr, preferably 40 to 80 ml/hr.
29,060B-F -3-i3~3040 To avoid the generation of water in the presence of hydro-gen it is necessary that oxygen be excluded from the reaction zone.
The exclusion of oxygen is preferably accomplished by sweeping out the reactor with an inert gas, e.g. nitrogen or carbon dioxide. If desired, the inert gas may contain hydrogen gas which serves to activate the catalyst. In any event, hydrogen will be present as the dehydrogenation reaction proceeds.
The inventions of both the parent and divisional applica-tions are further illustrated by the following examples.
Example 1 A mixture of pivalic acid (136 g, 1.33 mol) and 1,3-di-aminopropane (880 ml, 7.75 mol) was heated overnight at 225C in a stirred Parr reactor. After cooling and removal of the unreacted 1,3-diaminopropane by distillation, gas chromatographic analysis of the residue, a viscous oily material which was not stable to purifi-cation by distillation, showed a 90% yield of 3-aminopropylpivalamide.
The residue was diluted with o-xylene (250 ml) and the mixture refluxed for 48 hours in a Dean and Stark apparatus to effect cyclization-dehydration. After separation of the azeotrope, the o-xylene was evaporated to give 167 g (90% yield) of 2-t-butyltetra-hydropyrimidine having a melting point of 133 to 135C.
Example 2 A mixture of 25.5 g (0.25 mole) of trimethylacetic acid and 100 ml (112.6 g = 1.52 moles) of 1,3-diaminopropane was heated for 16 hours at 200-210C.
~3~3~0 After cooling and removing the excess 1,3-diaminopropane, the residue, 3-aminopropylpivalamide, a viscous oily material, was analyzed by NMR and gave a spectrum con-sistent with that expected for 3-aminopropylpivalamide.
A portion (1/2) of the above residue was allowed to react with an equivalent of each of tri-ethylamine and trimethylacetyl chloride at ambient temperature, the product was isolated by extraction with methylene chloride, washed three times with water, dried over MgS04, the solvent evaporated and the product crystallized on cooling. The filtered and dried product, N,N'-1,3-propandiylbis(2,2-dimethylpropanamide), 18.5 g, had a melting point of 120-122C, 93.6%. The NMR spectrum was identical to that of a sample prepared directly from 1,3-diaminopropane and trimethylacetyl chloride.
Analysis:
C13H26N202: C, 64.46; H, 10.74; N, 11 57 Found: C, 64.50; H, 11.02; N, 11.60 ExamPle 3 A solution of 70 g of 2-isopropyl-1,4,5,6--tetrahydropyrimidine in 100 ml of pyridine was fed at about 1 ml/min to a column 1" x 20" containing about 50 g of 0.5 percent platinum on a-alumina at 300 to 325C while sweeping ou~t the column with a mixture of nitrogen and hydrogen. The catalyst had been activated by passing a 2:1 H2~N2 stream over the bed for two hours.
The effluent was distilled giving 2-isopropylpyrimidine at 152 to 155C. The yield was 73 percent.
The above example was repeated employing varying amounts of 2-tertiarybutyl-1,4,5,6-tetrahydro-pyrimidine, varying amounts of solvents, 0.5 percent 29,060B-F -5-~3~3(~4~
palladium on alumina and temperatur~s of from 250 to 420C. The yields of 2-tertiarybutylpyrimidine ranged from 58 to 86 percent.
Similar results are obtained employing other solvents such as, for example, quinoline.
Example 4 91.6 g of 2-isopropyl-1,4,5,6-tetrahydropyri-midine was fed dropwise to the vapor phase dehydrogenator (1" x 20") with 50 g of 0.5 percent palladium on a-alumina over a two hour period while sweeping out the dehydro-genator with a stream of nitrogen and hydrogen. The reactor temperature was 310C. The product was distilled to give 67 g of product, b.p. 155C, yield 86 percent.
29,060~-F -6-
This divisional application is divided out of parent application serial no. 422,862 filed on March 4, 1983. The invention of this divisional application relates to a process for preparing 2-alkylpyrimidines. A further divisional application relates to the compound N,N'-1,3-propandiylbis(2,2-dimethyl-propanamide).
The invention of the parent application relates to 3-aminopropylpivalamide and a method of making it.
The preparation of tetrahydropyrimidines is discussed in "The Pyrimldines", Interscience (1962), page 445 ff. The preferred reaction involved refluxing 1,3-diaminopropane or a derivative with an alkyl ester of an organic acid, e.g., ethyl acetate or ethyl benzoate. However, when methyl pivalate was tried in this reaction, hydrolysis occurred and the resulting product was a complex mixture.
The tetrahydropyrimidines and particularly 2-t-butyl-tetrahydropyrimidine, are advantageously employed as precursors in the preparation of 0-alkyl-O[pyrimidine(5)yl]-(thiono)(thiol)-phosphoric(phosphonic)-acid esters or ester amides having exceptional insecticidal activity by the processes disclosed in, for example, United States Patent 4,127,652.
It has now been found that 3-aminopropylpivalamide can be prepared in high yields by contacting pivalic acid with 1,3-diaminopropane at temperatures above the boiling point of the 1,3-diaminopropane.
-` 13~304~
Removal of the unreacted 1,3-diaminopropane by distil-lation and dilution of the reaction mixture with a suitable solvent followed by refluxing provides 2-t-butyl-1,4,5,6-tetrahydropyrimidine in high yields.
The 3-aminopropylpivalamide prepared in this reaction is a novel compound as is N,N'-1,3-propan-diylbis(2,2-dimethylpropanamide) which is formed as a by-product. The 3-aminopropylpivalamide is advanta-geously employed to make 2-t-butyltetrahydropyrimidine which is an intermediate in the preparation of compounds having exceptional insecticidal activity.
The 3-aminopropylpivalamide is prepared by reacting pivalic acid with an excess of 1,3-diamino-propane at a temperature of 110 to 240C, preferably at 200 to 225C, for 3 to 12 hours. After removal of the unreacted 1,3-diaminopropane by distillation, the residue may be diluted with a suitable solvent and the resulting mixture refluxed, with or without pressure, at temperatures of 110 to 240C, preferably 170 to 190C, to provide 2-t-butyl-1,4,5,6-tetrahydropyrimidine.
Suitable solvents include those inert sol-vents which form azeotropes, thereby being useful to remove water from the reacting system, and have a boiling point of 110 to 240C at atmospheric condi-tions, or other inert s~lvents which will boil at 110to 240C under suitable pressure. Advantageously, - the solvent is toluene, o-xylene or diethylbenzene, although chlorinated benzenes such as monochlorobenzene and o-dichlorobenzene may be employed if desired.
29,060B-F -2-- 13~3Q~O
A 3 to 10 mole excess of 1,3-diaminopropane is usually employed, although larger molar excesses may be used, if desired. If less than a 3 molar excess is utilized, yields tend to be somewhat lower.
It has further been found that 2-t-butyl-pyrimidine, and other 2-alkylpyrimidines, can be prepared in high yields and purity in a simple one step reaction which comprises the dehydrogenation of a 2-alkyltetrahydropyrimidine under condltions which do not generate water and in which no water is added over a supported noble metal catalyst.
This reaction may be carried out neat, i.e., without employing a solvent, although an inert solvent such as, for example, pyridine may be advantageously employed.
The preferred catalysts are platinum and pal-ladium which are supported on, for example, silica gel, charcoal, activated carbon, magnesia or, pref~rably, alumina.
The reaction temperature is in the range of 250 to 450C, preferably 300 to 400C. Advantageously, the desired tetrahydropyrimidine, with or without sol-vent, is passed through a packed column containing the supported noble metal catalyst heated to the desired temperature. Feed rates to the vapor phase reactor, e.g., a 1" x 20" (2.5 x 51 cm) column containing 50 g of catalyst, are 20 to 150 ml/hr, preferably 40 to 80 ml/hr.
29,060B-F -3-i3~3040 To avoid the generation of water in the presence of hydro-gen it is necessary that oxygen be excluded from the reaction zone.
The exclusion of oxygen is preferably accomplished by sweeping out the reactor with an inert gas, e.g. nitrogen or carbon dioxide. If desired, the inert gas may contain hydrogen gas which serves to activate the catalyst. In any event, hydrogen will be present as the dehydrogenation reaction proceeds.
The inventions of both the parent and divisional applica-tions are further illustrated by the following examples.
Example 1 A mixture of pivalic acid (136 g, 1.33 mol) and 1,3-di-aminopropane (880 ml, 7.75 mol) was heated overnight at 225C in a stirred Parr reactor. After cooling and removal of the unreacted 1,3-diaminopropane by distillation, gas chromatographic analysis of the residue, a viscous oily material which was not stable to purifi-cation by distillation, showed a 90% yield of 3-aminopropylpivalamide.
The residue was diluted with o-xylene (250 ml) and the mixture refluxed for 48 hours in a Dean and Stark apparatus to effect cyclization-dehydration. After separation of the azeotrope, the o-xylene was evaporated to give 167 g (90% yield) of 2-t-butyltetra-hydropyrimidine having a melting point of 133 to 135C.
Example 2 A mixture of 25.5 g (0.25 mole) of trimethylacetic acid and 100 ml (112.6 g = 1.52 moles) of 1,3-diaminopropane was heated for 16 hours at 200-210C.
~3~3~0 After cooling and removing the excess 1,3-diaminopropane, the residue, 3-aminopropylpivalamide, a viscous oily material, was analyzed by NMR and gave a spectrum con-sistent with that expected for 3-aminopropylpivalamide.
A portion (1/2) of the above residue was allowed to react with an equivalent of each of tri-ethylamine and trimethylacetyl chloride at ambient temperature, the product was isolated by extraction with methylene chloride, washed three times with water, dried over MgS04, the solvent evaporated and the product crystallized on cooling. The filtered and dried product, N,N'-1,3-propandiylbis(2,2-dimethylpropanamide), 18.5 g, had a melting point of 120-122C, 93.6%. The NMR spectrum was identical to that of a sample prepared directly from 1,3-diaminopropane and trimethylacetyl chloride.
Analysis:
C13H26N202: C, 64.46; H, 10.74; N, 11 57 Found: C, 64.50; H, 11.02; N, 11.60 ExamPle 3 A solution of 70 g of 2-isopropyl-1,4,5,6--tetrahydropyrimidine in 100 ml of pyridine was fed at about 1 ml/min to a column 1" x 20" containing about 50 g of 0.5 percent platinum on a-alumina at 300 to 325C while sweeping ou~t the column with a mixture of nitrogen and hydrogen. The catalyst had been activated by passing a 2:1 H2~N2 stream over the bed for two hours.
The effluent was distilled giving 2-isopropylpyrimidine at 152 to 155C. The yield was 73 percent.
The above example was repeated employing varying amounts of 2-tertiarybutyl-1,4,5,6-tetrahydro-pyrimidine, varying amounts of solvents, 0.5 percent 29,060B-F -5-~3~3(~4~
palladium on alumina and temperatur~s of from 250 to 420C. The yields of 2-tertiarybutylpyrimidine ranged from 58 to 86 percent.
Similar results are obtained employing other solvents such as, for example, quinoline.
Example 4 91.6 g of 2-isopropyl-1,4,5,6-tetrahydropyri-midine was fed dropwise to the vapor phase dehydrogenator (1" x 20") with 50 g of 0.5 percent palladium on a-alumina over a two hour period while sweeping out the dehydro-genator with a stream of nitrogen and hydrogen. The reactor temperature was 310C. The product was distilled to give 67 g of product, b.p. 155C, yield 86 percent.
29,060~-F -6-
Claims
THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS
FOLLOWS:
1. A process for making 2-(isopropyl or tertiarybutyl)pyrimidines which comprises dehydrogenating a 2-(isopropyl or tertiarybutyl)-tetrahydropyrimidine in a vapor phase reactor, in the absence of oxygen and in which no water is added, over a supported noble metal catalyst.
2. Process of Claim 1 wherein the reaction is carried out at 250° to 450°C.
3. Process of Claim 2 wherein the catalyst is platinum or palladium supported on alumina.
29,060B-F -7-
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS
FOLLOWS:
1. A process for making 2-(isopropyl or tertiarybutyl)pyrimidines which comprises dehydrogenating a 2-(isopropyl or tertiarybutyl)-tetrahydropyrimidine in a vapor phase reactor, in the absence of oxygen and in which no water is added, over a supported noble metal catalyst.
2. Process of Claim 1 wherein the reaction is carried out at 250° to 450°C.
3. Process of Claim 2 wherein the catalyst is platinum or palladium supported on alumina.
29,060B-F -7-
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42387782A | 1982-09-27 | 1982-09-27 | |
| US458,812 | 1983-01-18 | ||
| US06/458,812 US4493929A (en) | 1981-09-14 | 1983-01-18 | Preparation of 2-alkylpyrimidines |
| CA000422862A CA1297498C (en) | 1983-03-04 | 1983-03-04 | Aminopropylpivalamides, method of preparation and use in making 2-t-butyl-1,4,5,6-tetrahydropyrimidine |
| US423,877 | 1989-10-19 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000422862A Division CA1297498C (en) | 1982-09-27 | 1983-03-04 | Aminopropylpivalamides, method of preparation and use in making 2-t-butyl-1,4,5,6-tetrahydropyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1303040C true CA1303040C (en) | 1992-06-09 |
Family
ID=27167332
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000579779A Expired - Fee Related CA1303040C (en) | 1982-09-27 | 1988-10-11 | N,n'-1,3-propandiylbis(2,2-dimethyl propanamide) and a process for preparing 2-alkylpyrimidines |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1303040C (en) |
-
1988
- 1988-10-11 CA CA000579779A patent/CA1303040C/en not_active Expired - Fee Related
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