CA1297498C - Aminopropylpivalamides, method of preparation and use in making 2-t-butyl-1,4,5,6-tetrahydropyrimidine - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

3-Aminopropylpivalamide is prepared by contacting pivalic acid with 1,3-diaminopropane at temperatures above the boiling point of 1,3-diaminopropane and the latter is distilled off. The residue may be refluxed to provide 2-t-butyltetrahydropyrimidine.

Description

~Læ~7~8 This invention relates to 3-aminopropylpivalamide and a method of making it. A divisional application, divided out of this parent application has been filed which relates to the compound N,N'-1,3-propandiylbis(2,2-dimethylpropanamide) and a process for preparing 2-alkylpyrimidines.
The preparation of tetrahydropyrimidines is discussed in "The Pyrimidines", 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-butyltetra-hydropyrimidine, are advantageously employed as precursors in the preparation of O-alkyl-O-~pyrimidin(5)yl~-(thiono)(thiol)-phos-phoric(phosphonic)-acid esters or ester amides having excep-tional 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-diamino-propane at temperatures above the boiling point of the 1,3-diamino-propane.

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`o'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.
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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 StPp reaction which comprises the dehydrogenation of a 2-alkyltetrahydropyrimidine under conditions 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 æolvent, although an inert solvent such as, for e~ample, 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, preferably, 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 S0 g of catalyst, are 20 to 150 ml/hr, preferably 40 to 80 ml/hr.

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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 at the dehydrogenation reaction proceeds.
The inventions of both the parent and the divisional applications are further illustrated by the following examples.
Example 1 A mixture of pivalic acid ~136 g, 1.33 mol) and 1,3-di-amlnopropane ~8~0 ml, 7.75 mol) WAS heated overnicJht at 225C in a stirred Parr reactor. AEter 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-aminopropylpival-amide.
The residue was diluted with o-xylene (250 ml) and the mixture refluxed for 48 hours in a Dean and Stark apparatus to e~fect cyclization-dehydration. After separation of the azeotrope, the o-xylene was evaporated to give 167 g (90% yield) of 2-t-butyl-tetrahydropyrimidine 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.

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~L297~9~8 , 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 prepaxed directly from 1,3-diaminopropane and trimethylacetyl chloride.
Analysis:
Calculated for 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 out the column with a mixture of nitrogen and hydxogen. 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-~97~

palladium on alumina and temperatures of from 250 to 420~C. The yields of 2-tertiarybutylpyrimidine ranged from 58 to 86 percent.

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Similar results are obtained employing other solvents such as, for example, quinoli.ne.

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'l) 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 o~ nitrogen and hydrogen. The reactor temperature was 310C. The produck was distilled to give 67 g o~ product, b.p. 155C, yield 86 percent.

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Claims (5)

1. 3-Aminopropylpivalamide.

2. A method for making 3-aminopropylpivalamide which comprises contacting pivalic acid with 1,3-diaminopropane in the absence of a catalyst at temperatures above the boiling point of the 1,3-diaminopropane and removing the excess 1,3-diaminopropane by distillation.

3. Method acoording to Claim 2 wherein the reaction is carried out at 110°C to 240°C.

4. Method according to Claim 3 wherein the reaction is carried out at 200° to 225°C.

5. Method according to Claim 2 wherein the 1,3-diaminopropane is present in from 3 to 10 molar stoichiometric excess.

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