JPH0789926A - Production of urea compounds or semicarbazide compounds - Google Patents

Abstract

PURPOSE:To obtain the compound in a high yield under almost neutral and mild conditions by reacting a hydroxamic acid compound with a specific haloiminium salt in the presence of a base and subsequently reacting the reaction product with an amine or hydrazine compound. CONSTITUTION:A hydroxamic acid compound of formula 2 (R<3> is organic group) is reacted with a haloiminium salt of formula 1 (R<1>, R<2> are lower alkyl; X is halogen; n is 2, 3) in the presence of a base of formula 4, and subsequently with an amine or hydrazine compound of formula 3 (R<4>, R<5> are H, organic group; Y is N, hydrazine bond) to obtain an urea or semicarbazide compound of formula 5. The method can industrially and advantageously provide the compound without being affected with the natures of the raw materials and without requiring to heat the raw materials at a high temperature. The resultant urea compound can be used in the fields of dyestuffs, fertilizers, antiparasitics, plastics, fibers, etc. The produced semicarbazide compound is important as a reagent for detecting aldehydes or ketones, and furthermore useful as a raw material for synthesizing heterocyclic compounds.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing ureas or semicarbazides, more specifically, hydroxamic acids are reacted with a haloiminium salt and amines or hydrazines to industrially advantageously produce ureas or semicarbazides. It relates to a method of manufacturing.

[0002]

Ureas are dyes such as pharmaceuticals,
It is used in the fields of fertilizers, anthelmintics, plastics, fibers, etc., and is also used as a raw material for the synthesis of carbodiimides (New Experimental Chemistry Course, Vol. 14, III, p162).
8). Further, semicarbazides are industrially useful compounds that are important as reagents for confirming aldehydes and ketones, and are also used as raw materials for synthesizing heterocyclic compounds (New Experimental Chemistry Lecture, Vol. 14, III, p1621).

Conventionally, as methods for producing such ureas, amines are added to cyanic acid, amines are added to isocyanates, amines are reacted with urea, carbamoyl chlorides and amines. There are known methods of reacting amines with amines and phosgene. As a method for producing semicarbazides, a method of adding hydrazines to cyanic acid, a method of adding hydrazines to isocyanates, a method of reacting ureas with hydrazines, a carbamic acid derivative and hydrazines A method of reacting with is known.

However, the method of addition reaction of cyanate with amines or hydrazines cannot be applied to the production of 3-position substituted ureas or 4-position substituted semicarbazides. In addition, in the method involving the addition reaction of isocyanates with amines or hydrazines, it is necessary to isolate isocyanates that are highly reactive, irritating and have a lacrimal property. The method by the condensation reaction of urea with amines or hydrazines requires reaction conditions at high temperature. The reaction of carbamoyl chlorides with amines and the reaction of carbamic acid derivatives with hydrazines are limited in the number of commercially available raw materials and their application range is limited. Furthermore, the reaction of phosgene with amines has the disadvantage that phosgene, which is highly toxic and corrosive, must be used.

[0005]

Therefore, there has been a demand for the development of a method for producing ureas or semicarbazides which is industrially advantageous without being affected by the properties of the raw materials and without the need for heating to a high temperature. .

[0006]

Under such circumstances, the present inventors have conducted diligent research to obtain a novel method for producing ureas or semicarbazides, and as a result, in the presence of a base in hydroxamic acids, the following general formula ( By reacting the haloiminium salt represented by 1) and then reacting with amines or hydrazines, the reaction can be carried out under almost neutral and mild conditions, and the ureas or semicarbazides can be produced in high yield. The inventors have found out what can be done and have completed the present invention.

The present invention is shown by the following reaction formula.

[0008]

[Chemical 2]

[Wherein, R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, n represents an integer of 2 or 3, R ³ represents an organic group,
R ⁴ and R ⁵ are the same or different and each represents a hydrogen atom or an organic group, Y represents a nitrogen atom or a hydrazine bond, and B represents a base]

That is, the present invention is characterized in that a hydroxamic acid (2) is reacted with a haloiminium salt (1) in the presence of a base (4), and then an amine or a hydrazine (3) is reacted. Alternatively, it provides a method for producing semicarbazides.

The haloiminium salt used in the present invention is represented by the general formula (1). In the formula, the lower alkyl group represented by R ¹ and R ² is a methyl group, an ethyl group, an n-propyl group, Isopropyl group, n-butyl group,
Examples thereof include linear or branched alkyl groups having 1 to 6 carbon atoms such as an isobutyl group. Further, examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom is particularly preferable. Specific preferred examples of the haloiminium salt (1) include 2-
Chloro-1,3-dimethylimidazolinium chloride, 2-chloro-1,3-dimethyl-3,4,5,6-
Examples thereof include tetrahydropyrimidinium chloride.

This haloiminium salt (1) can be obtained by, for example, adding an oxalyl halogenide, a phosphorus trihalide, a phosphorus pentahalide or an oxyhalogen to a compound represented by the general formula (6) which is known as an easily available solvent. It can be easily obtained by reacting a halogenating agent known per se such as phosphorus bromide, phosgene, trichloromethyl chloroformate and the like. In this reaction, either compound (6) or a halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride,
The other is added little by little to this, and the reaction is further carried out at room temperature to 70 ° C. for several hours to several tens of hours. The haloiminium salt (1) thus obtained can be isolated, but the reaction solution can also be used in the reaction of the present invention without isolation.

In the production method of the present invention, the raw material compound hydroxamic acid is not particularly limited, and for example, the general formula (2)
In, R ³ is an alkyl group which may have a substituent,
Examples thereof include alkenyl groups, aromatic groups, and heterocyclic groups. R ³ may have a substituent containing an ether bond or an olefin bond.

Examples of the base represented by B include 2,6-lutidine, pyridine, triethylamine and tributylamine.

To carry out the production method of the present invention, the haloiminium salt (1) is added to 1 mol of the hydroxamic acid (2).
After about 1 mol and about 2 mol of the base (4) are added and reacted at around room temperature, about 1 mol of the amines or hydrazines (3) may be added and further reacted at about room temperature.

The reaction solvent need not be used,
It is also possible to use a solvent that does not participate in the reaction, such as a halogenated hydrocarbon such as dichloromethane or dichloroethane, a hydrocarbon, an ether, or an aromatic hydrocarbon. Further, even when the reaction apparatus is carried out on an industrial scale, it is possible to use an ordinary stainless steel reaction kettle instead of a special reaction kettle such as glass lining.

In the production method of the present invention, since the haloiminium salt (1) is changed to the water-soluble compound (6), separation and purification are easy. Therefore, the desired ureas or semicarbazides can be isolated from the reaction mixture simply by a conventional method such as distillation or recrystallization.

[0018]

According to the production method of the present invention, ureas or semicarbazides can be efficiently produced from hydroxamic acids and amines or hydrazines under mildly neutral conditions.

[0019]

The present invention will be further described below with reference to examples, but the present invention is not limited thereto.

Example 1 Preparation of 1-n-butyl-3-phenylurea: 2.0 g of benzohydroxamic acid (15 mm) in 50 ml of methylene chloride.
ol) and 3.0 g (18 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and the mixture was stirred at room temperature until a homogeneous solution was formed. Then, under water cooling, 3.5 g (35 mmol) of triethylamine was slowly added dropwise, and after completion of the addition, the mixture was stirred for 40 minutes. 1.1 g (15 mmol) of n-butylamine was added dropwise to the reaction solution, and the mixture was stirred at room temperature for 2 days, then the solvent was concentrated under reduced pressure, and water and n-hexane were added to the obtained residue. The precipitated crystals were collected by filtration, washed successively with water and n-hexane and then dried to obtain 1.6 g of the title compound (yield 57%). mp .: 128.4-129.3 ° C., IR ν _max ^KBr cm ⁻¹ : 3390, 3310, 3260,
1650.

EXAMPLE 2 Preparation of 1-phenethyl-3-phenylurea: 2.0 g (15 mm) of benzohydroxamic acid in 50 ml of methylene chloride.
ol) and 3.0 g (18 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and the mixture was stirred at room temperature until a homogeneous solution was formed. Then, 3.5 g (35 mmol) of triethylamine was slowly added dropwise, and after completion of the addition, the mixture was stirred at room temperature for 30 minutes. 1.8 g (15 mmol) of phenethylamine was added dropwise to the reaction solution, and the mixture was stirred at room temperature for 18.5 hours, and then the same operation as in Example 1 was carried out to obtain 2.7 g (yield 78%) of the title compound. mp .: 154.3 to 155.0 ° C., IR ν _max ^KBr cm ⁻¹ : 3340, 3300, 1640.

Example 3 Preparation of 1,3-diphenylurea: 100 ml of methylene chloride
4.0 g (30 mmol) of benzohydroxamic acid and 5.9 g (35 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added thereto, and the mixture was stirred at room temperature until it became a homogeneous solution. Then, 7.1 g (70 mmol) of triethylamine was slowly added dropwise under water cooling, and after completion of the addition, the mixture was stirred at room temperature for 15 hours. Aniline 3.3 g (35
mmol) was added dropwise and the mixture was stirred at room temperature for 4 hours, and then the same operation as in Example 1 was carried out to obtain 4.4 g of the title compound (yield 66
%)Obtained. mp .: 242.5-243.1 ° C., IR ν _max ^KBr cm ⁻¹ : 3270, 3220, 1610.

Example 4 Preparation of 1-n-noyl-3-phenylurea: 2.0 g (1 part) of n-decanohydroxamic acid in 50 ml of methylene chloride.
1 mmol) and 2.2 g (13 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and the mixture was stirred at room temperature until a homogeneous solution was formed. Then, 2.6 g (26 mmol) of triethylamine was slowly added dropwise, and after completion of the addition, the mixture was stirred at room temperature for 30 minutes. After 1.2 g (13 mmol) of aniline was added dropwise to the reaction solution and stirred at room temperature for 20.5 hours, the same operation as in Example 1 was carried out to obtain 1.9 g of the title compound (yield 67%). mp .: 77.4 to 78.4 ° C, IR ν _max ^KBr cm ⁻¹ : 3325, 3290, 1625.

Example 5 Preparation of 1-cyclohexyl-3-phenylurea: 2.0 g (14 mmol) of cyclohexanecarbohydroxamic acid and 2.8 g of 2-chloro-1,3-dimethylimidazolinium chloride in 50 ml of methylene chloride. (17 mmol)
Was added, and the mixture was stirred at room temperature until it became a homogeneous solution. Then, 3.4 g (34 mmol) of triethylamine was cooled with water,
The solution was slowly added dropwise, and after completion of the addition, the mixture was stirred at room temperature for 30 minutes. 1.6 g (17 mmol) of aniline was added dropwise to the reaction solution,
After stirring at room temperature for 23 hours, the same operation as in Example 1 was carried out to obtain 2.1 g of the title compound (yield 70%). mp .: 186.4 to 187.4 ° C., IR ν _max ^KBr cm ⁻¹ : 3340, 1635.

Example 6 Preparation of 1,4-diphenylsemicarbazide: 2.0 g of benzohydroxamic acid (15 mm in 50 ml of methylene chloride)
ol) and 3.0 g (18 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and the mixture was stirred at room temperature until a homogeneous solution was formed. Then, 3.5 g (35 mmol) of triethylamine was slowly added dropwise under water cooling, and after completion of the addition, the mixture was stirred at room temperature for 30 minutes. 1.9 g (18 mmol) of phenylhydrazine was added dropwise to the reaction solution, and the mixture was allowed to stand at room temperature for 18 hours.
After stirring for an hour, the same operation as in Example 1 was carried out to obtain 2.2 g (yield 67%) of the title compound. mp .: 179.8-181.1 ° C., IR ν _max ^KBr cm ⁻¹ : 3340, 3290, 3210,
1660.

Claims (1)

[Claims] 1. Hydroxamic acids are represented by the general formula (1): [In the formula, R ¹ and R ² are the same or different and each represents a lower alkyl group, X is a halogen atom, and n is 2 or 3
The method for producing ureas or semicarbazides is characterized by reacting a haloiminium salt represented by the formula [1] in the presence of a base, and then reacting with an amine or a hydrazine.