Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2000-10-02
2002-01-01
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S136000, C564S138000, C564S153000, C564S155000, C564S159000, C546S189000
Reexamination Certificate
active
06335468
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an improved process for the production of N-acyl amino acid amide.
The N-acyl amino acid amide is employed for use application, such as an anti-oxidant, an additive agent for cosmetic preparations, an antistatic additive and an antimicrobial agent as an oil soluble nonionic surface active agent which is low toxic, low skin irritate and excellent in biodegradability. And, also it has a faculty or function to solidify an organic medium liquid at room temperature, in particular an inflammable organic medium, such as natural type of and synthetic type of mineral oils and animal and vegetable oils, and a nonflammable organic phosphorus compound and organochlorine based compound to the gel form, the agar gel form or the block form (Refer to Japanese Patent Kokoku Publications JP-B-51-42079, JP-B-53-13434 and JP-B-53-27776.), and therefore its industrial utility value in the gelatinizing agent for oils is noticed and watched.
DESCRIPTION OF THE RELATED ART
As the process for the production of N-acyl amino acid amide, the process for converting the carboxyl group in the N-acyl amino acid into an active group of high reactivity, such as that in an ester, an acid halide and an acid anhydride, and then reacting the thus obtained derivative thereof with an amine, the process for heating an N-acyl amino acid with an amine under dehydration to form an amide directly, and the like are known.
For the process for converting the N-acyl amino acid to an activated carboxylic acid derivative of which the carboxyl group has been converted into an active group of high reactivity, there are many descriptions in the literatures and the like, and therefore the suitable derivative can be selected by considering the reactivity of the N-acyl amino acid used as the starting material and the stability of the derivative obtained, and further in order to produce an objective N-acyl amino acid amide, it is essential to obtain the activated carboxylic acid derivative of the reaction intermediate at a high yield. For example, N-acyl amino acid ester can be produced in the condensation reaction under dehydration between an N-acyl amino acid and an alcohol, and however in order to obtain the N-acyl amino acid ester at a high yield, it is necessary to shift the equilibrium in the reaction by using the alcohol in a much excessive amount thereto, removing the water produced in the reaction, or the like, because the reaction is a typical equilibrium reaction. For one example therefor, the process for obtaining N-lauroyl-L-glutamic acid dimethy ester quantitatively in the reaction of N-lauroyl-L-glutamic acid with methanol in the presence of an acid catalyst using trimethyl orthoformate as the dehydrating agent is disclosed (Refer to Japanese Patent Kokai Publication JP-A-9-221461.), and further the process for producing N-lauroyl-L-glutamic acid di-n-butyl amide in the reaction of N-lauroyl-L-glutamic acid dimethyl ester with n-butylamine through an ester-amide exchange reaction is disclosed (Refer to Japanese Patent Kokai Publication JP-A-10-001463.). In the said process wherein an activated N-acyl amino acid derivative is produced as a reaction intermediate on route, the reaction proceeds with comparatively moderate condition and gives a good yield. And however, it has many reaction steps and burdensome in operations therefor, and therefore is disadvantageous in productivity as compared with the process for directly producing an amide (a direct amidation process), because it is necessary to remove surplus reaction solvent and dehydrating agent which have been used for the production of the reaction intermediate before proceeding to the amidation process. And, also there is a problem that 3 to 6 moles of the amine in surplus are necessarily used per 1 mole of the ester in order to carry out the amidation reaction smoothly.
As an example of the process for a direct amidation by heating a N-acyl amino acid with an amine to remove water, the process for obtaining N-acyl amino acid amide by heating directly N-acyl amino acid having acyl group(s) in the carbon number of 1 to 22 with an alkylamine in the carbon number of 8 or more, or the like to react them is known (Refer to Japanese Patent Kokoku Publication JP-B-52-18691.), and however, the process is difficult to be applied to the case where the alkylamine is one in the carbon number of 7 or less or an ammonia. That is, such known process corresponds to the process for obtaining an objective N-acyl amino acid amide which comprises mixing a N-acyl amino acid with an amine in the carbon number of 8 or more, and heating them directly at the temperature of 160 to 200° C. or heating them under reflux to remove water (dehydration) in the presence of an inactive solvent, such as xylene, and however the process has the following weak points (shortcomings). When the process is applied to the alkyl amine in the carbon number of 7 or less, or the like, the amine flies off under the condition of direct heating at the temperature of 160 to 200° C. or under the condition of heating in the presence of xylene or the like, because the boiling point of the amine is low, and therefore, the reaction yield is lowered. And, in the case where an amino acid residue in the N-acyl amino acid is one in the acidic amino acid and it has plural (two or more) carboxyl groups, the tendencies that one carboxyl group is easy to react, and on the other hand the other one is lowered in reactivity, are marked. To this end, in order to obtain a di- or tri-amide substitution derivative, they are reacted necessarily under a cruel (harsh) condition of a high temperature and a long time. Under such reaction condition, in addition to the condensation reaction between the objective carboxyl group and the amine, there are produced the secondary reactions, such as oxidation of the amine, an exchange reaction under condensation between an N-acyl group thereof and an amine, and a formation of nitrile to cause preparation of by-products (arisings). And, in the case where an optically active N-acyl amino acid is used as the starting material, because a racemization proceeds simultaneously, there are caused a problem that an objective optically active N-acyl amino acid amide is not obtained, and the like problem.
In order to improve the shortcomings (weak point) as described above, in a process for direct amidation of an N-acyl amino acid with a primary amine or an ammonia, the process wherein a boron compound as the catalyst coexists in the reaction thereof is disclosed (Refer to Japanese Patent Kokai Publication JP-A-61-00050.). By placing the catalyst coexistent, the reaction can be carried out at a low temperature and further the desired (objective) product can be obtained at a high yield as compared with the reaction without the catalyst. Moreover, since the reaction is carried out at a low temperature, the effects that a racemization is kept down and the like are obtained, even though an optically active N-acyl amino acid may be used as the starting material. However, the catalyst used in the reaction is soluble in water, and thus in the case where the reaction is carried out without a medium or in the hydrocarbon compound which is a medium for hylotropic (azeotropic) dehydration or a mixture thereof coexistent, the catalyst is not dissolved completely to give a system of the reaction heterogeneous, and the thus insoluble catalyst is deposited to the wall inside the reactor as scale buildup to account for (cause) bumping or the like. In addition, there is a problem that the reaction can not be accelerated and therefore a reaction time can not be shortened, because the insoluble catalyst can not be concerned with the reaction to lower the catalyst efficiency, while the amount of the catalyst added thereto is limited. And, in the reaction of an N-acyl amino acid with a secondary amine, according to such above process, the reactivity of the secondary amine is not accelerated sufficiently, and therefore the reaction does not proce
Hatajima Toshihiko
Tabohashi Tatsuru
Ajinomoto Co. Inc.
Davis Brian J.
Richter Johann
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