MXPA98000103A - Synthesis of n-acil-n-alquilcarboxila - Google Patents

Abstract

The chemical synthesis of N-acyl-N-alkylcarboxylates through the oxidation of substituted amides is formed of carboxylic acid esters and an N-alkyl-N-alkanolamate

Description

SYNTHESIS OF N * ACIL-N-AL0UILCARBOXILATOS FIELD OF THE INVENTION The present invention relates to the chemical synthesis of N-acyl-N-alkylcarboxylate compounds.

ATOCB SNT.ES PB LA INVEN, CT, QN The use of N-acyl-N-alkylcarboxylates with surfactants is well known. The combination of amido and carboxylate functional groups, coupled with the ability to incorporate a wide range of alkyl substituents, provides a highly desirable range of surfactant properties. Of this class of compounds, sarcosinates have the most extensive commercial application. Unfortunately, the synthesis of N-acyl-N-alkylcarboxylates in general, and of sarcosinates in specific, presents a cost relatively close to the application of the needs of the community of surfactants. The N-acyl-N-alkylcarboxylates have been historically synthesized, by reacting the sodium salt of an N-substituted amino acid with a fatty acid chloride in the presence of a strong base. The common industrial method of producing these fatty acid chlorides, includes the use of phosphorus trichloride. The fatty acid chlorides produced by this route tend to retain trace levels of inorganic or organic phosphorus compounds. These unpurified traces are often retained through subsequent steps and the lead darkens or becomes undesirable in the final product. Additionally the matter or substance is complicated, the N-substituted amino acids do not occur naturally as amino acids, and are indispensable to be produced using preferably severe conditions. For example, sarcosine, better known as ethylglycine, is produced by reacting acidic cyanide with formaldehyde to form a glycolic nitrile. This nitrile is then condensed with methylaminonitrile. The methylaminonitrile is hydrolyzed with a strong alkali to form the sarcosine salt. This synthesis is relatively expensive and undesirable unless the commercial attraction of the sarcosinates is widely used. The object of the present invention is to provide an alternative route for commercial purposes of compounds of the N-acyl-N-alkylcarboxylate class. The reaction sequences of the invention eliminate the use of N-substituted amino acids and acid chlorides. The hazardous chemical materials typically employed in, for example, the synthesis of sarcosine, such as formaldehyde, acidic cyanide, or all intermediary nitriles are omitted or avoided. The elimination of acid chlorides from the synthesis scheme also has the benefit of eliminating a source of problematic inorganic or organic phosphorus impurities from the final product. The present invention provides an alternative effective cost, direct by the synthesis of N-acyl-N-alkylcarboxylates of the formula PREVIOUS TECHNIQUE The following references are instructive; U.S. Patent 2,720,540, filed October 11, 1995, for the synthesis of sarcosine, Japanese Patent Sho61 ~ 216724, open to the public on September 26, 1987, for synthesis of sarcosinates from sarcosine with acid chlorides; U.S. Patent Nos. 3,836,551, filed September 17, 1974, and 4,380,646, filed April 19, 1983, for synthesis of N-acylamino carboxylic acids, esters and amines, and Jerry March, Advaced Qrqanic Chemistry 9- 22 (3rd ad 1985), for general discussion of the oxidation of alcohols to acids.

BRIEF DESCRIPTION OF THE INVENTION This development is related to a method for preparing -N-alkylcarboxylates and their salts, of the formula; (I) wherein R is a C ^ or higher hydrocarbyl substituent, R1 is a hydrocarbyl substituent of C - ^ - Cg, x is an integer from 1 to 6, and M is a cationic portion, preferably selected from metal salts alkaline and hydrogen, which comprises the steps of: (a) reacting in the presence of a base catalyst, an N-alkyl-N-alkanolamine of the formula wherein R1 and x are as described in the above; with a carboxylic acid ester of the formula wherein R is as described above, R2 is a C ^ or higher hydrocarbyl substituent, to subsequently form an N-acyl-N-hydroxyalkylamide of the formula; Y; (b) oxidizing the hydroxy group on the amide to a carboxy group; and (c) optionally neutralizing the N-acyl-n-alkylcarboxylate formed in step (b) to form the N-acyl-N-alkylcarboxylate (I) salt, therefore M is an alkali metal cation . The preferred method for preparing the amidation product of step (a) is brought to a temperature of about 80 ° C to about 200 ° C, and preferably at the reflux temperature, of the solution. More preferably, the reduced pressure is used, enough to maintain the reflux temperature from about 95 ° C to about 105 ° C. The carboxylic ester employed in step (a) has a hydrocarbyl group R of C1 to C24, preferably of Cg to C? G and more preferably of C12 to Clg. The substituent R2 can be methyl or ethyl, and more preferably is methyl. The process of step (a) may proceed with or without a suitable solvent. The solvents, preferably with boiling points below about 65 ° C and above about 200 ° C, can be used to facilitate the mixing of the reagents. More preferably the excess N-alkyl-N-alkanolamine can function as a solvent and can be recovered to be reused for a subsequent distillation of the reaction. To minimize or decrease the reaction time, it is preferred to use a basic catalyst such as alkoxide of sodium or potassium. The reaction of step (a) normally provides a yield of about 75% -90% theoretical basis in the amount of the ester employed with a molar ratio of reactive N-alkyl-N-alkanolamine to a reactive ester of about 20: 1 to about 1: 1, and a molar ratio of the reactive ester to a basic catalyst from about 0.05: 1 to about 0.2 to 1.

The amide product of step (a) is then used as a reagent for the oxidation of step (b). A variety of well-known oxidation methods can be employed to convert the functional alcohol to a carboxylic acid group, including, but not limited to the use of Na2-Cr2"° 7 in aqueous H2SO4" aqueous acetic acid, Cr03 / H2SO4 (reactive of Jone), pyridinium dichromate, and when the amide is free of any unsaturated alkyl substituent, Cr03 in pyridine, permanganates, nitric acid and oxygen with catalyst.The reaction is carried out in a solvent inert to the oxygenation conditions of the step (b), and preferably have a boiling point greater than about 100 ° C to facilitate work of the reaction mixture Preferably, the oxidation is carried out with the Jone Reagent and more preferably a mixture of dichloromethane and acetone as a solvent The preferred method for preparing the oxidation product of step (b) is carried out at a temperature of about 30 ° C to about 60 °, and more preferably from about 35 ° C to about 50 ° C. The reaction of step (b) usually provides a yield of about 85% to about 95% theoretical basis in the amount of the amide used.

The sarcosinate amino acid product of step (b) can optionally be converted to the amino acid sarcosinate salt by neutralization with an alkali metal base. All percentages, ratios and proportions of this are based on moles unless otherwise specified. All references are incorporated for reference.

DETAILED DESCRIPTION OF THE INVENTION The reaction sequence for the synthesis of a specific N-acyl sarcosinate is shown in the following. The reaction sequence, as illustrated, employs methyl laurate, sodium methoxide and chromic / sulfuric acid, but this is only an illustration and not a limitation, as will be seen later herein.

Methyl Laurate N-Metll-N-ethanolamine N-Methyl-N-ethanol lauramide N-Methyl-N-β-methanol lauramide N-lauroyl sarcosine The following is an illustration, and not a limitation of the conditions of the reagents, equipment and the like, useful in the instantaneous process. Amidation Reaction Process: The reactive carboxylic acid ester can be selected from alkyl esters (preferably methyl or ethyl) aliphatic straight-chain or unsaturated aliphatic acids, branched chain aliphatic, carboxylic ester and cycloaliphatic carboxylic acid. Non-limiting examples include methyl or ethyl esters of the following carboxylic acids: acetic, propionic, butyric, caprylic, caproic, monoic, decanoic, lauric, ironic, palmitic, stearic, oleic, linoleic, behenic, 2-methyl-undecanic, 2-butyl-actanoic, 2-ethyl-hexanoic, 3, 5, 5-trimethylhexanoic, and mixtures thereof. Methyl ester mixtures are derived from natural oils such as high oleic acid content (preferably having at least about 60%, more preferably at least 75%, and even more preferably at least about 90% of the oleic acid content ) are especially preferred. A solvent can be added to facilitate the mixing and dissolution of the reagents. It is preferred that the boiling point of the solvent be at least 200 ° C, it must be removed from the reaction product. It is further preferred that the solvent has a boiling point greater than about 65 ° C in order to allow the reflux temperature to be sufficient for the reaction to occur. Solvents such as, but not limited to, toluene, heptane, tetrahydrofuran, cyclohexane are suitable. Excess N-alkyl-N-alkanolamine is preferred as the solvent, since the excess will increase the reaction rate and can be further removed by distillation by or to be reused. A base with a pKa equal to, or greater than, the alkoxides is necessary to catalyze the amidation reaction. Various alkoxides are suitable such as sodium methoxide, potassium methoxide, sodium ethoxide, and potassium ethoxide. Bases capable of forming alkoxides from alcohols are also suitable, including the metal, the sodium metal, the potassium metal, sodium hydride and potassium hydride. Sodium methoxide is the preferred base. The reaction can be carried out under vacuum or under conditions of atmospheric reflux. The reaction temperatures will typically be less than about 65 ° C and greater than about 200 ° C. Reflux temperatures are used when they are less than about 120 ° C, the introduction of an inert gas such as argon, nitrogen or helium is useful for removing traces of atmospheric oxygen that may obscure lead in the reaction mixture. Preferably vacuum conditions are employed, as well as the lower reflux temperature of the reaction mixture. More preferably, vacuum conditions are employed, as well as the lower reflux temperature of the reaction mixture in the range of about 95 ° C to about 105 ° C and to remove the alcohol generated as the above reaction. The reaction times may vary of course, depending on the ratio of the reagents that have been used. However, as a general rule, a reaction time of about 4 to about 16 hours is sufficient. The stoichiometric reaction in the amidation step employs a molar ratio of reactive N-alkyl-n-alkanolamine to reactive ester of about 20: 1 to about 1: 1 and a molar ratio of reactive ester to basic catalyst catalyst of about 0.05: 1 at about 0.2 to 1. The reaction is terminated until the consumption of the reactive carboxylic acid ester, as determined by an analytical technique such as thin layer chromatography. Any excess N-alkyl-N-alkanolamine and solvent can be removed from the mixture by either atmospheric or vacuum distillation and recycled for later synthesis. The product can be obtained in purified form by conventional working methods, such as, dissolving the resultant amidation liquors in an organic solvent and washing with water to remove the basic catalyst. These organic liquors can be concentrated under vacuum to provide the product of amidation, typically at about 90% to 95% yield. Proof of the Oxidation Reaction: The amidation product is treated under sufficient oxidation conditions to convert the functional hydroxy of the substituted amide to a carboxylic acid. Oxidation methods include, but are not limited to the use of Na2_CR2-07 in H2S04 aqueous acetic acid, Cr03 / H2S04 (Jone Reagent), pyridinium dichromate, and when the R group of the amide is free of any substituent unsaturated alkyl, Cr03 and pyridine, KMn04, Zn (Mn04), nitric acid and oxygen with a catalyst. Preferably the Jone reagent was used to perform the oxidation. The reaction conditions for oxidation with the Jone reagent can be as follows. The product of amidation is stirred at room temperature in a solvent inert to the oxidation conditions of the Jone reagent. It is preferred that the solvent has a lower boiling point of about 100 ° C to facilitate removal by post-reaction distillation. Suitable solvents include but are not limited to acetone, dichloromethane, tetrahydrofuran, ethyl ether, and combinations thereof. A mixture of acetone and dichloromethane at about a ratio of 5: 1 is preferred. The reaction mixture is generally heated to about 35 ° C to about 50 ° C at which point the Jone reagent is added. Typically the Jone reagent is used in excess, in a molar ratio of the Jone reagent to the amidation product generally in the range of about 2: 1 to about 6: 1. Preferably, the molar ratio of the Jone reagent to the amidation product is in the range of about 3: 1 to about 5: 1. The reaction is typically rapid and usually ends in about 30 minutes to one hour. The reaction product can be worked under conventional conditions. During the oxidation of the Jone reagent, chromium salts are formed which can form gums in the reaction vessel. These salts can be dissolved by the addition of water during the work of the reaction. The addition of water forms two salts, which exist as aqueous layers and an organic layer. The aqueous layer can be drained and the organic layer washed repeatedly with additional water to remove unwanted salts. The organic layer can then be dried and concentrated to provide the final product in a typical yield in the range of about 85% to about 95% of the theoretical basis of the amount of amidation product used. Optionally, the resulting N-acyl-N-alkylcarboxylate can be converted to an alkali metal salt by neutralization with an alkali metal base, such as sodium or potassium hydroxide.

EXAMPLE I A. Synthesis of N-methyl-N-ethanol esteramide- A 250 ml two-necked round bottom flask is conditioned with a thermometer, a reflux condenser, a magnetic stirrer and a vacuum source vacuum aspirator. The reaction vessel is charged with methyl stearate (15.0 g, 0.05 mol.), N-methyl-N-ethanolamine (37.8 g, 0.50 mol) and potassium methoxide (0.7 g 0.01 mol) .The reaction is placed under vacuum cleaner and heated to 150 ° C while stirring.The reaction is maintained at 105 ° C under vacuum aspirator for 8 hours.The excess N-methyl, N-ethanolamine and the methanol residue is then distilled off under The reaction is cooled, dissolved in 200 ml of dichloromethane and washed with water twice.The dichloromethane layer is concentrated under vacuum and the desired product is obtained (14.5 g) • B. Synthesis of stearoyl sarcosine A flask of round bottom of three necks of 1 1, it is conditioned with a thermometer, a reflux condenser, and a mechanical agitator.The reaction vessel is charged with acetone (250 ml) dichloromethane (50 ml) and N-methyl, N-ethanol stearamide (5 g, 0.15 moles) The reaction mixture is stirred and heated to 38 ° C. or from Jone (8 ml, 8 N solution) is added in one portion with stirring. The reaction is allowed to stir for one hour at room temperature. Then water (100 ml) is added and the solution is diluted with dichloromethane (100 ml). The reaction mixture is transferred to a separate funnel 1 1 and the organic layer is washed three times with water (every 100 ml), dried and concentrated under vacuum to obtain the desired product (4.9 g). fiJSMP p U A. Synthesis of N-methyl, N-hydroxyethyl-seboamide- (NOTE tallow derivative of methyl ester of this example is composed of 70% octadecanoic and 30% hexadecanoic, hydrogenated methyl ester the ester composition having an average molecular weight of 289.5 g / mol). A 250 ml reaction flask is conditioned with a thermometer, the reflux condenser, an overhead stirrer, a heating blanket and a vacuum source passes to the condenser. The reaction flask is charged with tallow of methyl ester (20 g, 0.069 mol), N-methyl, N-ethanolamine (51.81 g, 0.69 mol), and potassium methoxide (0.8 g, 0.014 mol). The reaction is placed under vacuum and heated to 105 ° C while stirring. The methanol is removed by the reaction as its form. The reaction is run for eight hours while stirring at 105 ° C. The reaction is then removed by vacuum distillation to remove excess N-methyl, N-ethanolamine and any methanol residue. The reaction is then allowed to cool again to room temperature, then dissolved in dichloromethane. The solution is washed several times with water, then separated and dried under Na 2 SO. After remaining overnight, the solution is filtered to remove Na 2 SO 4 and stripped of electrons for a dry yield of 21.5 g of the desired product. B. Synthesis of seboil sarcosine A round neck flask with three necks of 1 1 is conditioned with a thermometer, a reflux condenser, a dropping funnel and a mechanical stirrer. The reaction vessel is charged with N-methyl, N-hydroxyethylseboamide (20.0 g, 0.06 mol, as prepared in step II A above) 300 ml of acetone and 50 ml of dichloromethane. The mixture is stirred and heated to 35 ° C. The chromic acid solution (Jone's Reagent, 30 mL of an 8N solution) is placed in the dropping funnel and added slowly to the reaction mixture while maintaining the temperature below 40 ° C. After the addition is complete and the chromium blue salt has precipitation. The reactor is stirred at room temperature for one hour. After one hour, the solution shows a slightly orange color of excess chromic acid. Isopropyl alcohol is added dropwise until the orange color disperses. The reaction mixture is diluted with water and 200 ml of dichloromethane. The mixture is transferred to a separate funnel, and the organic layer is washed several times with water. The washed organic layer is dried over anhydrous Na2SO4, filtered through a pad of celite and extracted under vacuum at a yield of 19.5 g of the desired product. The product is verified by I.R. spectroscopy.

EXAMPLE III A. Synthesis of N-methyl, N-hydroxyethyloleilamide A 250 ml reaction flask is conditioned with a thermometer, a reflux condenser, an overhead stirrer, a heating blanket and a vacuum source passes to the condenser. The reaction flask is charged with oleylmethyl ester (20.7 g, 0.07 mol), N-methyl, N-ethanolamine (52.5 g, 0.7 mol), and potassium methoxide (0.8 g, 0.014 mol). The reaction is placed under vacuum and heated to 100 ° C while stirring. The reaction is run for seven hours while stirring at 100 to 105 ° C. The reaction is then removed by vacuum distillation to remove excess N-ethyl, N-ethanolamine and any methanol residue. The reaction is then allowed to cool again to room temperature, then dissolved in 250 ml dichloromethane. The solution is washed several times with water. The organic layer is then separated and dried over Na2SO4. After remaining overnight, the solution is filtered to remove Na2SO4 and stripped of electrons for a dry yield of 23.0 g of the desired product. The product is verified by I.R. spectroscopy. B. Synthesis of olei sarcosine A 3-necked round bottom flask is conditioned with a thermometer, a reflux condenser, and a dropping funnel and a mechanical stirrer. The reaction vessel is charged with N-methyl, N-hydroxyethylseboamide (20.0 g, 0.0589 mol, as prepared in step III A above), acetone (300 ml) and 50 ml dichloromethane (50 ml). The mixture is stirred and heated to 35 ° C. The chromic acid solution (Jone's Reagent, 29.4 ml of an 8N solution) is placed in the dropping funnel and slowly added to the reaction temperature keeping below 40 ° C. After the addition is complete and the chromium blue salt has precipitation. The reactor is stirred at room temperature for 45 minutes.

A few drops of isopropyl alcohol is then added to remove the excess chromium acid. The reaction mixture is diluted with water and 200 ml of dichloromethane. The mixture is transferred to a separate funnel, and the organic layer is washed several times with brine. The organic layer is dried over anhydrous Na2SO4, filtered through a pad of celite and extracted under vacuum at a yield of 19 g of the desired product. The product is verified by I.R. spectroscopy.

Claims (8)

1. A method for preparing N-acyl-N-alkylcarboxylates and their salts of the formula (I) wherein R is a C- ^ or higher hydrocarbyl substituent, preferably Cg to C24, R1 is a hydrocarbyl substituent of C ^ Cg, preferably methyl or ethyl, x is an integer from 1 to 6, and M is an cationic portion, preferably selected from alkali metal salts and hydrogen, comprising the steps of: (a) reacting in the presence of a base catalyst, an N-alkyl-N-alkanolamine of the formula wherein R1 and x are as described in the above; with a carboxylic acid ester of the formula wherein R is as described above, R2 is a C-j_ or higher hydrocarbyl substituent, preferably cocoyl or derived seboyl, to subsequently form an N-alkyl-N-hydroxyalkylamide of the formula; and (b) oxidizing the hydroxy group on the amide to a carboxy group, preferably using an oxidation method selected from the group consisting of methods used Nao2Cr207 in aqueous H2SO4, Nao2Cr207 in aqueous acetic acid Cr03 / H2SO4 (Reagent from Jone ), pyridinium dichromate, KMn04, Zn (Mn04) 2, nitric acid and oxygen with catalysis; and (c) optionally neutralizing the N-acyl-N-alkylcarboxylate formed in step (b) to form the N-acyl-N-alkylcarboxylate (I) salt, therefore M is an alkali metal cation .

2. The method according to claim 1, characterized in that the reaction step (a) is limed by alkoxide base preferably selected from the group consisting of sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, t-butoxide of sodium, potassium t-butoxide, and mixtures thereof.

3. The method according to any of the preceding claims, characterized in that the N-alkyl-N-alkanolamine in the reaction step (a) is N-methyl-N-ethanolamine.

4. The method according to any of the preceding claims, characterized in that the reaction step (a) uses a solvent selected from the group consisting of excesses of N-alkyl-N-alkanolamines, toluene, heptane, tetrahydrofuran, and cyclohexane; preferably excess N-methyl-N-ethanolamine.

5. The method according to any of the preceding claims, characterized in that the reaction step (a) uses a molar ratio of N-alkyl-N-alkanolamine to carboxylic acid ester of greater than 1 to less than 20.

6. The method according to any of the preceding claims, characterized in that the carboxylic acid ester contains at least 60% oleic acid ester.

7. The method according to any of the preceding claims, characterized in that the reaction step (b) uses a solvent with a boiling point below 100 ° C, preferably selected from the group consisting of acetone, dichloromethane, tetrahydrofuran, ethyl ether, and mixtures thereof.

8. The method according to any of the preceding claims, characterized in that the reaction step (a) uses a molar ratio of N-methyl-N-ethanolamine to carboxylic acid ester of greater than 1 to less than 20.