JPH0359897B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides monosubstituted urea and alkylene diamine compounds in a solvent having the formula R ₁ OH, where R ₁ is hydrogen or alkyl having 1 to 4 carbon atoms. The present invention relates to an effective method for selectively producing a urea-alkylenediamine adduct.

The preparation of aminoalkylurea compounds from urea and alkylene diamine compounds generally involves extensive multi-step processes or the use of hazardous auxiliaries such as cyanic acid and its salts. In quite a number of cases, these conventional manufacturing methods include steps for removing hydrochloric acid or nitric acid from the reaction product after the reaction is complete or precautions that require careful handling of the reactants before or during the reaction. therefore, they do not lead to efficient large-scale production of aminoalkylurea compounds. It is also known from US Pat. No. 2,145,242 that dialkylurea compounds can be prepared by heating urea and polyethylene diamine at elevated temperatures in solvents with relatively high boiling points such as phenols, cresols and hydroxydiphenyls. There is. Not only do disubstituted alkyl amines form in these solvents at elevated temperatures, in part from rapid decomposition of the urea, but also the high temperatures required to remove these solvents accelerate the decomposition of monosubstituted aminoalkylureas. Therefore, this method is not useful in the present invention.

Therefore, no convenient and economical method existed for the selective production of aminoalkylureas by condensation of urea with alkylene diamines. The aminoalkylureas produced according to the present invention are inter alia
Useful as an intermediate in the manufacture of beta-adrenergic inhibitors, such as those described in pending U.S. Patent Application No. 320,773 entitled "2-Hydroxypropylamine Aryl Ester Derivatives" by Tsam Kam and William L. Matier It is.

According to the invention, the formula A method is provided for making a compound having the formula: wherein A is a branched or straight aliphatic hydrocarbon chain having from 2 to 10 carbon atoms. The process of the present invention comprises combining a diamine having the formula H ₂ N-A-NH ₂ (wherein A has the meaning given above) with urea and a diamine having the formula R ₁ OH (wherein R ₁ is hydrogen or 1
alkyl having ~4 carbon atoms) at a condensation temperature and then removing the solvent.

The method according to the invention uses the formula An aminoalkylurea having the formula H ₂ N-A-
from alkylene diamine compounds with NH ₂ (wherein A is a branched or straight aliphatic hydrocarbon chain with 2 to 10 carbon atoms) in urea and a solvent with a relatively low boiling point. This is a method of selective production by condensing until the reaction is completed and then removing the solvent by evaporation. In stark contrast to the methods conventionally used for the production of aminoalkylureas, the method of the present invention does not require washing away hydrochloric or nitric acid from the reaction product once the reaction is complete, nor does it require washing away the isocyanate salt or its derivatives. Its use is also unnecessary.

The method of the invention is based on the formula (In the formula, R ₂ and R ₃ are each hydrogen or 1
lower alkyl having ~4 carbon atoms;
and n is an integer from 1 to 10). These compounds have the formula is formed by heating a diamine having the formula R ₁ OH with urea in a solvent having the formula R 1 OH, where R ₁ is hydrogen or alkyl having 1 to 4 carbon atoms.

In accordance with one of the embodiments of the present invention, the alkylene diamine compound has 2 to 10 primary amino groups.
compounds separated by linear aliphatic hydrocarbon radicals having 2 to 6 carbon atoms, preferably 2 to 6 carbon atoms, such as ethylenediamine, propylenediamine, tetramethylenediamine, pentamethylenediamine, etc.; Compounds separated by branched aliphatic hydrocarbon groups having ~10 carbon atoms, preferably 3 to 6 carbon atoms, such as 1-methylethyl diamine, 2-methylethylene diamine, 1,1 -dimethylenediamine, 1,2-dimethylenediamine, 1,1-diethylenediamine, and the like.

According to the invention, the reaction can be carried out using urea.

In accordance with the present invention, the reactants are heated to a temperature sufficient to condense the urea and the primary diamine without decomposition of the reactants with concomitant liberation of ammonia. It is preferred to use a condensation temperature of about 60 DEG to about 120 DEG C., and more preferred is a condensation temperature of about 60 DEG to about 100 DEG C. Although it is not necessary that the solvent be heated to its boiling point during the reaction, methods of refluxing urea and alkylene diamine in a solvent with a boiling point within this temperature range have been shown to be advantageous for the production of monosubstituted diamines. It has been discovered and provides an advantageous method according to the present invention.

Solvents according to the present invention include, but are not limited to, those having the formula R ₁ OH, where R ₁ is hydrogen or lower alkyl. When R ₁ is not hydrogen, alkyl having 1 to 4 carbon atoms is preferred. Therefore, in addition to water, lower alcohols such as methanol, ethanol, n-propanol, isopropanol, butanol, and isobutyl alcohol are useful as solvents in the method of the present invention. It has been found that water and isopropyl alcohol provide excellent yields of aminoalkylureas by the process of the present invention. These solvents not only facilitate the monosubstitution of diamines in accordance with the present invention, but are also advantageous for removal from the completed reaction vessel without the need for elevated temperatures that would cause decomposition of the aminoalkylurea product. Something was discovered. Even if heated at lower temperatures during the reaction of urea with diamine, solvents with relatively high boiling points require that the solvent be removed from the reaction vessel at elevated temperatures upon completion of the reaction, and the May cause decomposition.

According to the invention, the condensation of urea with the corresponding diamine is allowed to proceed until ammonia evolution ceases. The generation of ammonia from the reflux reaction can be easily measured by measuring the pH of the effluent using a condensation column. Reaction times useful for completion of the reaction include, but are not limited to, about 10 to 24 hours. However, the duration of the reaction will vary depending on the solvent and the temperature to which the solvent is heated.

In accordance with the present invention, it has been found that varying amounts of urea and alkylene diamines can be used without affecting the selective monosubstitution of diamines.
For example, both 1:1 and 2:1 molar ratios of urea to alkylene diamine can be used, both ratios yielding the same monosubstituted product. Furthermore, about
urea at a concentration of 2.5 to about 6.2 mole/and about 2.5 to about
The same product can be produced in excellent yield using a concentration of 5.7 mol/diamine.

The following examples illustrate specific embodiments of the invention and are not intended to limit the scope of the invention.

Example 1 This example uses the formula This shows the synthesis of the compound.

1,2-diamino-2-methyl-propane
88.16g (1 mole) and 60.6g (1 mole) of urea
was refluxed in 176 ml of deionized water at 100 °C for 10 h,
Evaporate to an oil and azeotrope with dioxane (remove residual water) to produce a dry white solid. This white solid is dissolved in 350 ml of warm ethyl acetate, cooled for 3 hours, then crystallized under an atmosphere of _N2 , filtered, washed with 100 ml of ethyl acetate and dried under reduced pressure at 60 °C, melting point: 88-90 A product with a temperature of 57% is obtained (yield: 57%). NMR and IR spectra are consistent with the above structure and chemical analysis is consistent with the empirical formula (C45.96; H9.94; N31.93).

Example 2 This example uses the formula This shows the synthesis of the compound.

1,2-diamino-2-methyl-propane 529
(6 mol) and 397 g (6.6 mol) of urea are refluxed in 1058 ml (828 g) of isopropanol at 82° C. for 24 hours. Evaporate to oil, dioxane 1
evaporated to an oil at 75° C., dissolved in ethyl acetate, cooled and then crystallized under N ₂ atmosphere. Washing with 10% isopropanol 1 in ethyl acetate and drying at 65° C. under reduced pressure gives a product with the same physical and chemical properties as the product of example 1 (yield: 67.2%).

Example 3 This example uses the formula This shows the synthesis of a compound having

30g (0.5mol) of ethylenediamine and urea
30 g (0.5 mol) in 200 ml of isopropanol 82
Reflux for 24 hours at °C. Evaporate to an oil, filter, add oxalic acid, filter, redissolve in ethyl acetate, cool, then crystallize, melting point: 148
A white powder with a temperature of ~150 °C is obtained (yield: 58%).
NMR and IR spectra are consistent with the above structure,
and chemical analysis is consistent with the empirical formula (C31.12;
H5.67; N21.68).

Example 4 (Reference example) In this example, the formula This shows the synthesis of the compound.

1,2-diamino-2-methyl-propane 8.8
g (0.1 mol) and urea 6.0 g (0.1 mol) 125
Reflux for 5 hours (net) at °C. Ethanol-
Dissolve in an ethyl acetate mixture, filter, cool to 0°C, filter, wash with ethyl acetate and then dry in an oven to obtain a compound with a melting point: 175-177°C. NHR and IR spectra are consistent with the above structure.

Example 5 (Reference example) In this example, the formula This shows the synthesis of a compound having

1,2-diamino-2-methyl-propane 8.8
(0.1 mol) and 6.0 g (0.1 mol) of urea are heated in 20 g of phenol in an oil bath for 3 hours.
Cool to room temperature, dissolve in 100 ml of ethyl acetate, decant, dissolve in 50 ml of ethyl acetate, decant again, dissolve in a mixture of ethyl acetate and ethanol, filter, cool to 0 °C, filter, add acetic acid Washing with ethyl and then with ether and then drying in Ouvre gives a compound with a melting point of 175-177°C (yield: 81.6%). NMR and IR spectra are consistent with the above structure, and chemical analysis is consistent with the empirical formula (C41.30; H7.96; N32.31).

Example 6 (reference example) Example 5 except for using 12.1 g (0.2 mol) of urea
Repeat all the basic processes. The compound produced (yield: 82.7%) is the same as that of Example 5.

Although the invention has been described in detail and with particularity with respect to preferred embodiments thereof, it will be understood by those skilled in the art that modifications may be made thereto without departing from the spirit and scope of the invention.

Claims (1)

[Claims] 1 formula (wherein A is a branched or straight aliphatic hydrocarbon chain having 2 to 10 carbon atoms), the method comprises: H ₂ N-A-NH ₂ in which A has the meaning given above is condensed with urea in a solvent having the formula R ₁ OH, in which R ₁ is hydrogen or alkyl having 1 to 4 carbon atoms. A process consisting of reacting at a temperature followed by removal of the solvent. 2. The process of claim 1, wherein the diamine is refluxed with urea in a solvent having the formula R ₁ OH, where R ₁ is hydrogen or alkyl having 2 to 4 carbon atoms. 3. The method of claim 1, wherein the diamine is refluxed with urea in water or isopropanol. 4. The method of claim 1, wherein A is a branched or straight hydrocarbon chain having 2 to 6 carbon atoms. 5. The method of claim 4, wherein the diamine is refluxed with urea in a solvent having the formula R ₁ OH, where R ₁ is hydrogen or alkyl having 2 to 4 carbon atoms. 6 formula (wherein R ₂ and R ₃ are each hydrogen or lower alkyl having 1 to 4 carbon atoms, and n is an integer from 1 to 10), (wherein R ₂ , R ₃ and n are as defined above) and urea and a diamine compound having the formula
R ₁ OH (wherein R ₁ is hydrogen or alkyl with 1 to 4 carbon atoms) in a solvent at the condensation temperature and then removing the solvent. Method in section 1. 7. The process of claim 6, wherein the diamine is refluxed with urea in a solvent having the formula R ₁ OH, where R ₁ is hydrogen or alkyl having 2 to 4 carbon atoms. 8. The method of claim 6, wherein the diamine is refluxed with urea in water or isopropanol. 9. The method of claim 6, wherein _R2 and _R3 are each hydrogen, methyl or ethyl, and n is an integer from 1 to 5. 7. The method of claim 6, wherein 10 R ₂ and R ₃ are each hydrogen or methyl, and n is 2 or 3. 11. The process of claim 9, wherein the diamine is refluxed with urea in a solvent having the formula R ₁ OH, where R ₁ is hydrogen or alkyl having 2 to 4 carbon atoms. 12. The method of claim 6, wherein R ₂ and R ₃ are each hydrogen or methyl, n is 1, and R ₁ is hydrogen or propyl.