JPH01172367A - Production of oxyalkylcarbamate compound - Google Patents

Abstract

PURPOSE:To readily and safely obtain the title compound useful as an intermediate for medicine and agricultural chemicals in high yield, by reacting a system consisting of a specific oxyalkylamide, a basic compound and alcohol with halogen. CONSTITUTION:A system consisting of oxyalkylamide expressed by formula I [R is (substituted)alkyl or (substituted)aryl], basic compound (e.g. NaOH, KOH, sodium methylate) and alcohol, e.g. the formula R<7>OH [R<7> is (substituted) alkyl] is reacted with a halogen (e.g. Br, Cl or I) to provide the oxyalkyl carbamate expressed by formula II [R' is same as R; R<2> is (substituted)alkyl].

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a method for producing a carbamate compound useful as an intermediate raw material for medicines and agrochemicals. Specifically, it provides a method for producing an oxyalkyl carbamate compound from an oxyalkyl amide.

<Prior art and problems to be solved by the invention> For carbamate compounds having an alkoxyalkyl group, an aryloxy group, etc., a method based on the following reaction is known (British Patent No. 1,279, 412
(1972)).

■ R'OH+ R'0CHzCHJCOR'0CHz
CHJHCOR'■R'OCX + R'0C1hCH
zNTo Rb0CHzCHzNHCOR' (However,
R3, R4, 8% and R6 are the same or different alkyl groups having up to 6 carbon atoms, alkenyl groups, cycloalkyl groups, aryl groups, etc. Moreover, X is chlorine, bromine, or iodine. ) However, the synthesis method of the above carbamate compound is
Each has the following drawbacks. That is, the isocyanate compound used in the reaction (2) has a pungent odor and is easily polymerized, and must be handled with great care. Furthermore, the halogen carbonate esters used in the reaction (2) are highly irritating and easily hydrolyzed compounds, so great care must be taken when handling and storing them. Furthermore, both compounds are generally known to be extremely toxic to living organisms. As mentioned above, the conventional synthesis of carbamate compounds has various drawbacks,
It was also very disadvantageous industrially.

<Means for Solving the Problems> As a result of extensive research into a method for producing oxyalkylamides that is easy to operate and industrially advantageous, the present inventors have developed a method using a specific oxyalkylamide as a raw material. The inventors have discovered that oxyalkyl carbamate compounds can be produced safely and in high yield through a specific reaction, and have completed the present invention.

That is, the present invention provides an oxyalkylamide represented by the general formula (1) (wherein R is a substituted or unsubstituted alkyl group or a substituted or unsubstituted alkyl group), General formula (n) characterized by reacting a halogen with a system consisting of a basic compound and an alcohol (wherein, R' is the same as R in general formula (1)).

R2 is a substituted or unsubstituted alkyl group. This is a method for producing oxyalkyl carbamate 1ff shown in ).

The oxyalkylamide, which is a raw material used in the present invention, is a compound represented by the general formula (1) (where R is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group). It is. In the above - Arson CI), the alkyl group represented by R is not particularly limited, and a linear or branched group may be used. In particular, a lower alkyl group having 1 to 6 carbon atoms is preferred.

Typical examples include methyl group, ethyl group, n-propyl group, n-butyl group, 1so-butyl group,
Examples include cyclohexyl group. Also, - arson (1)
Among them, the alkyl group represented by R may be substituted with a substituent, and the type of the substituent is not limited in any way as long as it does not interfere with the reaction, and one can be used depending on the object. For example, a substituted or unsubstituted alkenyl group having 2 to 6 carbon atoms; a substituted or unsubstituted alkynyl group having 2 to 6 carbon atoms; a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms; Examples thereof include a substituted or unsubstituted narkylthio group; a substituted or unsubstituted haloalkyl group having 1 to 6 carbon atoms; a substituted or unsubstituted phenyl group; a substituted or unsubstituted naphthyl group, and the like.

More specific examples of representative substituents include allyl group, 2
-Methylallyl group, 2-methylallyl group, -methylallyl group, 2-propynyl group, 2-butynyl group, 1-butenyl group, 2-butenyl group, 2-methoxyethyl group, 2-
Ethoxyethyl group, 2-methylthioethyl group, 2-chloroethyl group, 2-bromoethyl L 2,2-dichloroethyl group, 2-fluoroethyl group, phenyl group, 4-phenylsulfonylphenyl group, 2-methoxyphenyl group, 4 -Carbamoylphenyl group, 4-chlorophenyl group, 4-methylphenyl group, 3,4-dimethylphenyl group, 4-nitrophenyl group, 4-cyanophenyl group, 4-
Acetyl phenyl group, 4-methoxycarbonylphenyl group, 2-naphthyl group, 2-(4-methylnaphthyl group, 1
-(2-methylnaphthyl group, etc.) Furthermore, in the -arson (I), the aryl group represented by R can be used without particular restriction.Also, the aryl group may be substituted with a substituent. The type of the substituent is not limited in any way and can be used as required.Specific examples include phenyl group, 4-chlorophenyl group, 4-promophenyl group,
4-fluorophenyl group, 3-fluorophenyl group, 4
-nitrophenyl group, 4-methylsulfonylphenyl group, 2-hydroxyphenyl group, 4-ethylphenyl group,
4-methylphenyl group, 3,4-dimethylphenyl L4
-ter-butylphenyl group, 4-trifluoromethylphenyl group, 4-carbamoylphenyl group, 4-methoxycarbonylphenyl group, 4-cyanophenyl group, 4-
methoxyphenyl group, 3,4-dimethoxyphenyl group,
3,4-dimethoxyphenyl group, 4-acetylphenyl group, 2,6-dimethylphenyl group, 2,6-dimethoxyphenyl group, 2,4-dichlorophenyl 15.2- /
Examples include f-4-chlorophenyl group.

Further, the basic compound used in the present invention is not particularly limited, and bases generally used in the Hoffman reaction can be used. Specific examples of the basic compounds preferably used include alkali hydroxides such as sodium hydroxide and potassium hydroxide, metal alcoholade waters such as sodium methylate, sodium ethylate, potassium methylate, and potassium ethylate. Examples include barium oxide.

Among these basic compounds, especially from an industrial point of view,
Alkali hydroxide is suitable because it is easy to handle and inexpensive.

The amount of the basic compound used is preferably selected from a range of 2 to 5 equivalents, preferably 2 to 2.8 equivalents, per equivalent of the oxyalkylamide represented by the general formula (1). When the amount of the basic compound used is less than the above range, side reactions tend to occur and the yield of the target oxyalkyl carbamate compound tends to decrease.On the other hand, when it is more than the above range, the amount of the basic compound used is more likely to occur after the reaction. Neutralization of a large amount of the basic compound is required, which is not only uneconomical, but also tends to cause decomposition of the raw materials and decrease the yield of the target product.

In the present invention, alcohol is used as a single ignition R'OH... (
III) ' (However, R2 is a substituted or unsubstituted alkyl group.) Above-
In arson (III), the alkyl group represented by R7 is not particularly uniform, and a linear or branched group is used.

In particular, a lower alkyl group having 1 to 5 carbon atoms is preferred.

Specific examples of representative groups include methyl group, ethyl group, 1so-propyl group, n-butyl group, and n-pentyl group. In addition, the alkyl group represented by R7 in the -arson (I For example, a substituted or unsubstituted alkoxy group having 1 to 6 carbon atoms;
Substituted or unsubstituted alkylthio group having 1 to 6 carbon atoms;
Examples include substituted or unsubstituted haloalkyl groups having 1 to 6 carbon atoms. More specific examples of typical substituents include 2-methoxyethyl group, 2-ethoxyethyl group, 2-ethoxyethyl group,
-Methylthioethyl group, 2-chloroethyl group, 2-bromoethyl group, 2,2-dichloroethyl group, 2-fluoroethyl group, 3-methoxypropyl group, 2-methoxypropyl group, 3-ethoxypropyl group, 2-ethoxy Propyl group, 3-methylthiobrobyl group, 3-methoxybutyl group, 2-ethoxybutyl group, 2-methoxypentyl group,
Examples include 3-methoxyhexyl group.

In the present invention, it is particularly preferable to use an alcohol in which R7 is an unsubstituted alkyl group as a raw material in order to achieve a high yield in the reaction.

As such alcohol, readily available and inexpensive methanol and ethanol are suitable.

The ratio of alcohol to the oxyalkylamide shown in the above-mentioned - Arson (1) is preferably 1 equivalent or more relative to 1 equivalent of the oxyalkylamide. In other words, if the amount of alcohol used is less than the above percentage,
Unreacted substances of oxydialkylamide, which is another raw material, remain, which is economically disadvantageous.

In addition, the above-mentioned oxyalkylamides, basic compounds,
and an alcohol, it is preferred to use a solvent. As such a solvent, alcohols such as methanol, ethanol, and n-propanol can usually be used. In addition, - is one of the raw materials in the above reaction.
Excessive use of alcohol indicated by arson (Iff);
It is particularly preferable that the solvent also serves as a solvent in order to obtain the target product in high yield.

Examples of the halogen used in the present invention include bromine, chlorine and iodine, with bromine and chlorine being particularly preferred.

The amount of the above-mentioned halogen to be used is preferably selected from a ratio of 1 to 5 equivalents, preferably 1 to 2.5 equivalents, per equivalent of the oxyalkylamide represented by 2[). If the amount of halogen used is less than the above range, it will be economically disadvantageous because unreacted substances will remain.On the other hand, if the amount used is too large, a large amount of halogen will remain after the reaction, which will require a complicated process to remove. Some operations may be required.

In the present invention, it is important to react the halogen with the system consisting of the above-mentioned oxyalkylamide, basic compound, and alcohol. That is, by reacting a halogen with the above system, an oxyalkyl carbamate compound can be obtained for the first time in a high yield.

Further, the halogen may be supplied in a gaseous or liquid form, or may be dissolved in a solvent.

In the present invention, reaction conditions are not particularly limited, but generally the reaction temperature is preferably selected from the range of -80 to 80°C, preferably 0 to 20°C. Also,
Preferably, the reaction is carried out under stirring.

Furthermore, in the present invention, the oxyalkyl carbamate compound produced may be isolated if necessary. The method for isolating such a carbamate compound is not particularly limited, and any known method can be employed. For example, after the reaction is complete, add acid to make the hydrogen ion concentration 6.0 to 7.5, and then for 1 to 2 hours.
The desired product is obtained by heating and maintaining at 50 to 60°C, cooling to room temperature, filtering, and distilling the residue under normal pressure or vacuum. In addition to purification by distillation, if the product is a solid, it can also be purified by recrystallization.

〔effect〕

As understood from the above explanation, according to the present invention, by reacting specific raw materials in a specific reaction order, it is possible to obtain an oxyalkyl carbamate compound safely, in high yield, and through easy reaction operations. can. Moreover, the obtained carbamate compound is useful as an intermediate for chemical substances such as agricultural chemicals, and can be easily converted into an amine compound by hydrolysis.

〔Example〕

EXAMPLES In order to explain the present invention more specifically, Examples are given below, but the present invention is not limited to these Examples.

Example 1 300 rnl equipped with stirrer, thermometer and reflux condenser
Put 30.9 g of 3-methoxypropionamide, 24.0 g of sodium hydroxide, and 150 g of methanol into a three-necked flask, cool to 5°C, and add bromine 4 while stirring.
7.9 g was added dropwise over 1 hour.

After the dropwise addition was completed, the temperature was gradually raised to 20°C, and after stirring at this temperature for 1 hour, residual methanol was distilled off by atmospheric distillation. Water was added to the resulting residue, and then extracted with ether to obtain an extract. After distilling off the ether from the extract, the residue was distilled under reduced pressure to obtain N-(2-methoxyethyl)carbamic acid. Methyl (b, p 73-74.5
40.3g (yield 82.0%)
)Obtained.

Example 2 In the same manner as in Example 1, oxyalkylamides shown in Table 1 were reacted with various alcohols and halogens to synthesize oxyalkyl carbamate compounds. The reaction conditions and yields are shown in Table 1.

Table 1 Table 1 Continued 1 Table continued 1 Table continued 1 Table continued 1 Table continued 1 Table continued Example 3 In a 300 ml three-neck flask equipped with a stirrer, thermometer, and reflux condenser. Add 150 g of methanol to the solution, carefully add 14.0 g of sodium (after adding over 2 hours,
Add 30.9 g of 3-methoxypropionamide;
The mixture was cooled to 5° C., and 47.9 g of bromine was added dropwise over 1 hour while stirring. After completion of the dropwise addition, the temperature was gradually raised to 20°C, and after stirring at 20°C for 1 hour, methanol was distilled off by atmospheric distillation. By adding water to the residue, extracting with ether, distilling off the ether, and distilling the residue under reduced pressure,
Methyl N-(2-methoxyethyl)carbamate (b,
p, 74-75℃ 10.19 Dragon Hg) to 34.9g (
Yield: 71.0%).

Example 4 In the same manner as in Example I, a reaction was carried out by changing the ratios of methanol, sodium hydroxide, and bromine to 1 equivalent of 3-methoxypropionamide as shown in Table 2. The results are also shown in Table 2.

Table 2 Comparative Example 1 In Example 1, the reaction was carried out by reversing the order of addition of 3-methoxypropionamide and bromine, and 20.7 g of methyl N-(2-methoxyethyl)carbamate was obtained (yield: 42
．． 1%) was obtained.

Application example 1 300 rnl equipped with stirrer, thermometer and reflux condenser
73.5 g of ethyl N-(2-ethoxyethyl)carbamate and 1001R1 of water were placed in a three-necked flask, and 100M1 of a 20% aqueous sodium hydroxide solution was added over 1 hour, followed by heating for 2 hours with stirring. After refluxing, it was cooled. After extraction with ether and distilling off the ether under normal pressure, the residue was distilled under normal pressure to obtain 80.0 g (yield: 89.5%) of 2-ethoxyethylamine (b, p98-104°C).

Claims (1)

[Claims] (1) General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼...[I] (However, R is a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group.) General formula [II] characterized by reacting a halogen with a system consisting of an oxyalkylamide, a basic compound, and an alcohol [II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼... [II] (However, R' is the same as R in the general formula [I]. R^2 is a substituted or unsubstituted alkyl group.