MXPA97001988A - Procedure for preparing n-lauroil-l-glutamil-di-n-butilam - Google Patents

Abstract

The present patent application relates to a process for preparing N-lauroyl-L-glutamyl-di-n-butylamide by reaction of dimethyl N-lauroyl-L-glutamate with n-butylamine, characterized in that the reaction is carried out in the presence of a hydrocarbon or mixture of hydrocarbons as a solvent

Description

PROCEDURE FOR PREPARING N-LflUROYL-L-GLUTflrlIL-DI-N-BUTILRMIDfl DESCRIPTION OF THE INVENTION The present patent application relates to a process for preparing N-lauroyl-L-glutamyl-di-n-butylanide rnedian + reaction of N-lauroyl-L-glu + arna + or d rnet it with n-butylamine in the presence of a hydrocarbon or mixture of hydrocarbons as dissolved and authorized. N-laroyl-L-glutamyl-din-n-butylamide has been repeatedly described in the paten + literature as a thickener for apolar and hydrophobic media in most cases, but this compound has been defined as a thickener. It is excellent for making pressure-sensitive paper, photosensitive printing plates, butane-based "solid fuel" and vulcanized products, for thickening residual solutions of photographic development and for various cosmetic applications, for example lipsticks. The properties of the product, considered very useful for these applications, however, are extremely inconvenient in their manufacture. This refers above all to the realization of an acceptable process from the ecological and economic point of view, which can lead to a product of pure purity with high yields, without producing large quantities of waste and wastewater.

To obtain amides of the carboxylic and dicarboxylic acids, there are in the literature many routes of sufficiency sufficingly cited. According to each case and depending on the reactivity, it is possible to start from the various carboxylic acid derivatives, such as, for example, chlorides, anhydrides, esters or also other amides. The variant chloride route, the most promising in terms of reaction and yield, does not apply in this case because the chloride of N-luroyl-L-glistatic acid is very difficult to obtain. The direct condensation ifl of the carboxylic acids with amines usually requires more drastic conditions, such as working at high temperatures or high pressure. The preparation of N-lauroyl-L-glutamyl-di-n-butylamide by direct condensation is described in document CO 105 (17), 153544 (1986) 5 (corresponding to 3P 61 00050 fl?). However, in this case, the applicant's own tests gave only yields between 40 and 60%, so that the product still usually contained a large amount of impurities. The reaction of the carboxylic acids with 0 amines is usually carried out in an inert solvent or in the alcohol of the ester. Normally an excess of amine is used, in order to be able to carry out a complete transformation. If the product can not be easily crystallized or recrystallized, it is isolated by tra + armen-to in aqueous phase, generally producing large amounts of waste water containing amine and alcohol, which means, by experience, many stages of purification.

The reaction of N-lauroyl-L-glutamate di-ethyl with n-butylamma seems very difficult and the subsequent purification is fraught with problems. In many inert solvents, for example co-aromatics or toluene, but also in glycols, esters, etc. N-lauroyl-L-glutamyl-di-n-butylanide - it certainly tends to gel and to include impurities, especially of n-butyl amine, which as already said is used in excess. Therefore, the aforementioned solvents can not be used. Due to the above-mentioned properties, it is almost impossible to find suitable solvents to purify the product by recrystallization. If, consequently, once the reaction is finished, an aqueous phase preparation is chosen, a fairly free product of butylamine is obtained, of acceptable purity and yield, but at the expense of great effort and large quantities of wastewater which, together with various impurities of the organic type contain the excess of butylamma used in the synthesis as well as the rnetanol released when the amide is formed. Therefore, there is an urgent need for a way to synthesize N-lauroyl-L-glutapu 1-d? -n-but? Lam? Da, that does not present the inconveniences previously exposed. Now, surprisingly, it has been discovered that starting from the di-ethyl N-lauroyl-L-glutamate, a very pure N-lauroyl-L-glutamyl-di-n-butylamide, practically free of butylamine, can be obtained if the reaction is carried out in the presence of a hydrocarbon or a mixture of hydrocarbons as an auxiliary solvent. In this way, the diester can be simply transformed into the diamide with partial removal, favored by the reaction, of the methanol liberated and the product can be procd and isolated without problems. For convenience, n-butylannine is added in excto the N-lauroyl-L-glutamate of dirnetyl. Preferably, 2.1 grams of 10 moles of amine are added per mole of ester, especially between 3 and 6 moles of amine. In this way, n-butylane acts simultaneously as a solvent. The hydrocarbons or mixtures of hydrocarbons used as auxiliary solvents preferably have boiling points higher than 60 ° C, especially above 100 ° C. Examples of suitable hydrocarbons are n-nonane, n-decane, n-udecane, n-dodecane, as well as cyclohexane derivatives with various alkyl groups, boiling above 100 ° C, such as trirnethylcyclohexane, rilethylethylcyclohexane and diethylcyclohexane. Suitable mixtures of hydrocarbons are, above all, those of the aforementioned hydrocarbons, especially high-boiling ciciohexane derivatives. Such mixtures are known to the specialists and are commercially available. The hydrocarbons or their mixtures are preferably used in amounts of from 20 to 300% by weight, in particular from 50 to 150% by weight, based on the N-lauroyl-L-glutathione of dirnethyl. Once the transformation of the reactants is finished, the product is finished and separated.

In a preferred embodiment of the process of the present invention, the excess of n-butylarnine is first removed by distillation and then the product is precipitated by adding a polar solvent. Suitable polar solvents are, above all, alcohols, ethers, esters and alkanols, for example acetone. If a hydrocarbon or hydrocarbon mixture with a sufficiently high boiling point is selected for the reaction, in particular above 100 ° C, then the n-butyl-amine (boiling point 77.8 ° C) can be recovered through a column and eventually reused. Even after removing the n-butylamma, the reaction mixture remains manageable without increasing too much viscosity. To precipitate the product it is convenient to use + the amount of the polar solvent that does it completely and t + l + abie. After precipitation, the product is filtered and, if desired, washed with more solvent. With these washes the already small proportion of impurities can be further reduced. In general according to the process of the present invention, the purity of the obtained product is > 95%, typically even > 97%. The dimethyl N-lauroyl-L-glutamate necessary as starting material is a compound known from the literature and can be prepared by methods known to the skilled worker.

EXAMPLE 1 In 1 1 1 Quickfit flask, with glass-coated thermal probe, gas inlet, stainless steel anchor stirrer and heatable pre-heater (67-7Q ° C) with overlapping Claisen bridge, followed by condensation trap, are introduced under a light current of N2 110 g of N-lauroyl-L-glutathione di-methyl (LGR-DME) and 100 g of a mixture of cyclohexane derivatives (ethylcyclohexane, methylethylcyclohexane, diethylcyclohexane in an approximate ratio of 45: 25: 10 ). In the interval of 30 minutes, 110 g of n-butylarnine are metered in and heated to reflux. During the reaction, part of the rnetanol liberated in the binding, with some n-b-tilamine, is separated through the tempered precolumn. After about 8 hours of reflux, control by DC indicates that the reaction has been quantitative. The excess of n-butylamine is distilled first under normal pressure, then under vacuum and the product is precipitated by adding acetone. The resulting precipitate is filtered under vacuum, washed with acetone, dried and triturated. The desired product is obtained, N-lauroyl-L-glutamyl-di-n-butyl-amide, with good yield of approximately 80% and with excellent purity (99% of LGB (HPLC), 50 ppm of nBuNH? (GC), < 1% other impurities) in the form of a colorless powder with a melting point of 150-152 ° C.

COMPARATIVE EXAMPLE In a 1 1 Ouickfit flask, with glass-lined thermal probe, gas inlet, stainless steel anchor stirrer and reflux condenser, a slight current of 2 110 g of N-lauroyl-L-glutarna or of dirnetyl (LGA-DME) in 20 ge MeOH. In the interval of 30 minutes, 110 g of n-butylamma are metered in and heated to reflux for 8 h. The reaction mixture is dissolved in 100 g of rnetanol and 400 g of water are added, with which the gelatinous product precipitates. To achieve, among others, the values of residual butyrannine, it is prepared as follows: The resulting pasty precipitate is filtered under vacuum, stirred with 300 g of 1 N HCl, washed with 2 x 250 g of water until pH 3, stir with 2 x 300 g of 1N NaOH and finally wash with about 2000 g of water until the filtrate gives a neutral reaction. The resulting dough is dried and crushed. The desired product is obtained, N-lauro-L-glutarin-l-d-n-b-ti-lamide, with a yield of approximately 70% and with medium purity (78% of LGB (HPLC), 180 ppm of nBuNH2 ( GC), 5% lauroyl butyl ida (HPLC),> 15% other impurities) in the form of a fairly colorless powder with a melting point of 135-145 ° C. The large quantities obtained from wastewater must be treated.

Claims (7)

NOVELTY OF THE INVENTION CLAIMS

1. - Process for preparing N-lauroyl-L-glutarnil-di-n-butylamide by reaction of N-lauroyl-L-glutamate of dirnetyl with n-butylamine, characterized in that the reaction is carried out in the presence of a hydrocarbon or a mixture of hydrocarbons as an auxiliary solvent.

2. Process according to claim 1, characterized in that from 3 to 6 moles of n-butyla ine are used per mole of N-laruoyl-L-glutamate of dirnetyl.

3. Process according to claim 1 and / or 2, characterized in that hydrocarbons or mixtures of hydrocarbons with a boiling point higher than 100 ° C are used.

4. Process according to one or more of claims 1 to 3, characterized in that hydrocarbons or mixtures of hydrocarbons are used n-nonane, n-decane, n-undecane, n-dodecane or derivatives of cyclohexane with various alkyl groups, boiling points above 100 ° C.

5. Process according to one or more of claims 1 to 4, characterized in that the hydrocarbons or hydrocarbon mixtures are used in amounts of 50 to 150% by weight with respect to the N-lauroyl-L-glutamate of dirnet.ilo.

6. Process according to one or more of claims 1 to 5, characterized in that, once the reaction is finished, the excess of n-butylamine is removed by distillation and then the N-lauroyl-L-glutamyl-di-n is precipitated. -butylamide by adding a solvent or mixture of polar solvents.

7. Process according to claim 6, characterized in that acetone is used to precipitate N-la? Roi1-L-gl? Tarni1-di-n-butylanide.