EP1247880B1 - Process for the preparation of glycine derivatives - Google Patents

Abstract

Preparation of glycine derivatives comprises electrochemically oxidizing the hydroxide groups of beta -hydroxyethylammonium compounds to yield the corresponding acid.

Description

The invention relates to a novel process for the preparation of glycine derivatives. Glycine derivatives such as betaines are known as mild and compatible substances and are used in large quantities for the production of cosmetic preparations for the cleansing and care of skin and hair.

Glycine derivatives are prepared by the processes known in the art by reacting tertiary amines with excess monochloroacetic acid in excess in basic aqueous solution at elevated temperature.

Great efforts have been made in the past to produce glycine derivatives that are free of contaminants that may cause skin irritation or otherwise be undesirable for toxicological and physiological reasons.

These include in particular the process-related residual amounts of compounds with organically bound chlorine, such as monochloroacetic acid (MCA) and in particular dichloroacetic acid (DCA) or salts thereof, which are introduced with the chloroacetic acid used in the final product.

Attempts to reduce the content of these compounds by prolonged reaction times or by increasing the pH did not lead to a significant reduction. The use of pH values above about 10 brings the risk of a particular at elevated temperatures at or above 100 ° C. increasing decomposition ( DE-B-29 26 479 . EP-B-0 557 835 ).

The DE-A-39 39 264 relates to a process for lowering the residual content of free alkylating agent in aqueous solutions of amphoteric or zwitterionic surfactants, characterized in that the solutions are aftertreated with ammonia, an amino acid having 2 to 8 C atoms or an oligopeptide. This residual treatment also leaves a residual content of MCA and / or DCA in the reaction product. In addition, however, the reaction products of ammonia and alkylating agent or peptide and alkylating agent produce reaction products which remain as impurities in the process product.

Furthermore, the reaction mixtures contain large amounts of chloride ions in the form of their alkali or ammonium salts. Thus, they have other disadvantages such as increasing the viscosity of the final product, adversely affecting the low temperature stability of formulations, and they can not be formulated with a number of other active ingredients.

Furthermore, they are due to the chloride ion content too aggressive for the cleaning of corrosion-sensitive metallic substrates such as those used in particular in the electronic industry.

There have therefore been a number of attempts to remove these salts, such as by solvent extraction as in US Pat JP-A-59075998 described or by electrodialysis according to EP-A-0 269 940 , Apart from the fact that complete removal of the chloride ions can not be achieved, these processes are complicated by the additional steps required and economically disadvantageous.

There are numerous methods that allow the oxidation of alcohols to carboxylic acids. In addition to the classical methods of oxidation on a laboratory scale by means of heavy metal oxides (eg KMnO ₄ ), there are also processes which can be carried out on an industrial scale, such as the oxidation by NO ₂ ( US-A-5,856,470 ), by nitrile oxides ( US-A-5,179,218 ), by O ₂ under noble metal catalysis ( DE-39 29 063 ) or electrochemically ( EP-A-0 199 413 . DE-A-34 43 303 ).

From works by H.-J. Schäfer it is known (overview: Topics in Current Chemistry, 1987, 142, 102 to 129) that primary alcohols by electrolysis in alkaline solution using nickel oxide with NiO (OH) coated anodes and steel cathodes with yields between 46 and 99% of theory (i.e., Th.) Can be oxidized to the corresponding carboxylic acids. The oxidation is carried out mainly by an indirect anode process in which the alcohol is oxidized by the nickel oxide with trivalent nickel to the carboxylic acid, wherein the NiO (OH) is reduced to nickel oxide or nickel hydroxide with 2wertigem nickel. By electron removal at the anode, the 2-valent nickel is then converted back into the 3-valent nickel.

About the electrochemical oxidation of alcohols which are bound via an ethylene group to a quaternary positively charged nitrogen, is not reported in the above work.

In an effort to overcome the shortcomings of the prior art and to provide a process which enables the production of glycine derivatives, it has now been found that this objective is achieved by the oxidation of quaternary amino alcohols. Surprisingly, the quaternary, positively charged nitrogen does not disturb the oxidation process, and it can neither oxidation products of nitrogen, such as N-oxides, nor degradation products according to Hoffmann be detected. Glycine derivatives prepared in this way are free of inorganic chlorine and organically bound chlorine, in particular monochloroacetic acid, dichloroacetic acid and their salts.

The oxidation of the quaternary amino alcohol to the corresponding glycine derivative can be carried out by electrochemical oxidation in aqueous alkaline solution using coated nickel electrodes.

The present invention therefore relates to a process for the preparation of glycine derivatives by oxidation of β-hydroxyethylammonium compounds by electrolysis of an aqueous alkaline solution, which is characterized in that the oxidation is carried out using nickel oxide hydroxide-coated anodes.

The method is characterized by extraordinary environmental friendliness, since on the one hand no polluting by-products are incurred and on the other hand can be dispensed with the use of highly toxic chloroacetic acid. In addition, a product is obtained directly free of inorganic chlorine, so that can be dispensed with a technically complex separation of the chloride ions.

By the electrochemical process yields are consistently greater than 80% d. Th. Received. The electrolysis is in principle carried out so that the aqueous electrolyte is electrolyzed on nickel oxide hydroxide coated electrodes. The coating of the electrodes can be carried out according to customary methods such as, for example, the method proposed by HJ Schäfer. In principle, a Ni (OH) ₂ layer is first cathodically deposited from a Ni salt solution on the later anode and then converted anodically in alkaline solution to NiO (OH) ( J. Kaulen, HJ Schaefer, Tetrahedron, 1982, 38, 3299 ).

As the anode materials to be coated with NiO (OH), besides nickel metal, other materials to which the activated nickel oxide hydroxide layer is adhered, such as Monel, stainless steel, graphite or glassy carbon, may be used.

The cathode may be made of any material commonly used in electrochemistry for the manufacture of cathodes, such as precious metals, stainless steel or nickel.

The electrolysis cell may consist of any material resistant to electrolyte and reactants, such as alkali-resistant glass, porcelain, polyethylene, rubber or stainless steel.

The cell type may be divided or undivided, with the latter being preferred, since no reduction of the desired electrolysis product must be feared.

The process according to the invention can be carried out continuously or batchwise, the process preferably being carried out batchwise. In this mode of operation, the electrolysis system consists of an aqueous solution of the β-hydroxyethylammonium compound having a pH preferably above 12. The alkalinity of the solutions is generally effected by alkali metal hydroxides (preferably NaOH and KOH). The necessary for the neutralization of the resulting acid liquor is added gradually, with slightly less than the theoretically necessary amount is added, so that the pH of the solution obtained after completion of the electrolysis is about 9.

Advantageous levels of β-hydroxyethylammonium compound of the alkaline solution are between 1 and 30 wt .-%, preferably between 20 and 30 wt .-%.

The electrolysis temperature is usually 20 to 80 ° C, preferably about 70 ° C.

It is also expedient to carry out the electrolysis with a higher than the theoretically required amount of electricity, preferably 1.5 to 3 times the amount of electricity.

After completion of the electrolysis, the electrolyzed solution is brought to pH 6 to 7, for example with phosphoric acid, concentrated and the residue extracted with a suitable solvent. For this purpose, e.g. Alcohols (ethanol, isopropanol) suitable. The resulting extract is freed from the solvent and gives the pure betaines.

The extraction is only necessary if the salt-free betaines are to be obtained. Usually, however, do not interfere with the resulting salts in the synthesis, so that can be dispensed with an extraction.

The β-hydroxyethylammonium compounds used in accordance with the invention can be prepared by reaction of amines with ethylene oxide in acidic solution by the processes known in the art ( EP-A-0 098 802 ).

in welcher die Reste

R

unabhängig voneinander Alkylreste mit 1 bis 3 C-Atomen und/oder -CH₂-CH₂-OH sein kann und

n,m,o

Werte zwischen 1 bis 5, vorzugsweise 1 bis 3, insbesondere 1 sein können, und

R¹

ein gegebenenfalls Heteroatome, inbesondere Sauerstoff- und/oder Stickstoffatome enthaltender Alkylrest oder der Rest R^a-[C(O)-NH-(CH²) _q]_r- mit q = 1 bis 6, vorzugsweise 2 oder 3, und r = 0 oder 1, ist.

As β-hydroxyethylammonium compounds, all compounds which contain at least one quaternary amino group and at least one OH group, preferably of the formulas (I) and / or (II) and / or (III), can be used

in which the radicals

R

independently of one another can be alkyl radicals having 1 to 3 C atoms and / or -CH ₂ -CH ₂ -OH and

n, m, o

Values between 1 to 5, preferably 1 to 3, in particular 1 may be, and

R ¹

an optionally heteroatom, in particular oxygen and / or nitrogen atoms containing alkyl radical or the radical R ^a - [C (O) -NH- (CH ² ) _q ] _r - with q = 1 to 6, preferably 2 or 3, and r = 0 or 1, is.

Preferred compounds according to the invention are compounds in which the free valencies of the general formula (I) are bonded to the radical R ^a -C (O) -NH, where R ^{a is} an optionally substituted alkyl or alkenyl radical having 7 to 21 C atoms or optionally substituted alkyl or alkenyl radical having 1 to 22 carbon atoms, preferably having 7 to 17 carbon atoms, and the radicals R may be independently of one another alkyl radicals having 1 to 3 carbon atoms; or when r = 0, R ^{a can be} an alkyl or alkenyl radical having 8 to 22 C atoms; Valences of the general formulas (I) to (III) are bonded to an optionally substituted alkyl or alkenyl radical having 1 to 22 C atoms, preferably having 8 to 18 C atoms or on the radical R ^{a is} -C (O) - [NH- (CH ₂ ) _z ] _y - in which R ^{a has} the abovementioned meaning, and z, y can independently of one another be numbers from 1 to 3; in which the free valencies of the general formula (IV) are bonded to the radical R ^a , as defined above.

The radical R ^a is preferably derived from natural fatty acids, such as caprylic acid, capric acid, 2-ethylhexanoic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, isostearic acid, stearic acid, hydroxystearic acid (ricinoleic acid), dihydroxystearic acid, oleic acid, linoleic acid, petroselinic acid, elaidic acid, arachidic acid, Behenic acid and erucic acid, gadoleic acid and the technical mixtures obtained in the pressure splitting of natural fats and oils, such as oleic acid, linoleic acid, linolenic acid and in particular rapeseed oil fatty acid, soybean oil fatty acid, sunflower oil fatty acid, tall oil fatty acid. In principle, all fatty acids with a similar chain distribution are suitable.

The content of these fatty acids or fatty acid esters in unsaturated proportions is - as far as necessary - adjusted by the known catalytic hydrogenation to a desired iodine value or achieved by mixing fully hydrogenated with non-hydrogenated fat components.

The iodine number, as a measure of the average degree of saturation of a fatty acid, is the amount of iodine absorbed by 100 g of the compound to saturate the double bonds.

Preferably, partially cured C _8/18 coconut or palm oil fatty acids, rapeseed oil fatty acids, sunflower oil fatty acids, soybean oil fatty acids and tall oil fatty acids, with iodine numbers in the range of about 80 to 150 and in particular technical C _8/18 coconut fatty acids are used, it being possible where appropriate for a selection of cis / trans isomers, such as elaidic acid C _16/18 fatty acid cuts, to be advantageous. They are commercial products and are offered by various companies under their respective trade names.

The compounds of the general formulas (I) to (III) are oxidized electrochemically to the corresponding acids as described below.

Example 1:

To a mesh electrode (60.5 cm ² , NiO (OH) coated nickel mesh) and a cathode (cylinder, Ø 1.7 cm, 7 cm high, stainless steel) were in a 150 ml beaker cell with reflux condenser 105 ml of a 27% solution of 2-hydroxyethyl (dimethyl) 3-undecylcarboxamidopropylammonium x 0.5 H ₂ PO ₄ ^- containing 4.2 g of NaOH, electrolyzed for 7 h at a current of 2.0 A. During this time, the pH rose to 8 to 9 within 5 h, and 4 ml of saturated NaOH solution were added. The current was then adjusted to 1.0 A and electrolyzed for a further 7 h. After this time, the solution again has a pH of 8 to 9, and 4 ml of saturated NaOH solution are added again. Subsequently, a current of 0.5 A is set and electrolyzed for a further 7.5 h. The resulting solution has a pH of 8 to 9. The reaction was monitored by TLC chromatography and ESI mass spectrometry.

The Elektrolyseaustrag is adjusted with phosphoric acid to a pH of 6 to 7 and concentrated. The residue is extracted with isopropanol and the extract obtained freed from the solvent. The product gives a yellow-brown solid.

analytics

Yield: 23.3 g (91% of theory)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ = 13.67 (CH ₃ ), 22.24 to 31.48 (CH ₂ ), 35.86 and 35.87 ( C H ₂ CONH and CONH C H ₂ ), 50.32 (N ⁺ (CH ₃ ) ₂ ), 62.12 (CH ₂ N ⁺ ), 63.98 (N ⁺ C H ₂ COO ^- ), 167.09 (COO ^- ), 174.06 (CONH) ppm.

Example 2:

The experiment was carried out analogously to Example 1. In contrast to Example 1, 2-hydroxyethyl (dimethyl) 3-undecylcarboxamidopropylammonium x 0.5 C ₂ O ₄ H ^{- was used} as starting material. During the oxidation, oxalate is first oxidized to CO ₂ , which reacts under the alkaline conditions to carbonate and only then oxidizes the ammonium alcohol to the corresponding glycine derivative. The correspondingly larger amount of NaOH required was added to the solution from the beginning.

analytics

Yield: 20.28 g (82% of theory)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ = 13.39 (CH ₃ ), 21.95 to 31.18 (CH ₂ ), 35.55 (br, C H ₂ CONH and CONH C H ₂ ) , 50.15 (N ⁺ (CH ₃ ) ₂ ), 61.77 (CH ₂ N ⁺ ), 63.73 (N ⁺ C H ₂ COO ^- ), 165.81 (COO ^- ), 173.65 (CONH ) ppm.

Example 3:

The experiment was carried out analogously to Example 1. In contrast to Example 1, 105 ml of a 2.7% solution of an ammonium mixture (based on the Kokosfettsäureschnitt) containing as the main component, the 2-hydroxyethyl (dimethyl) 3-undecylcarboxamidopropylammonium x 0.5 H ₂ PO ₄ ^- , for 3 h electrolysed at 2.0 A.

analytics

Yield: 2.35 g (96% of theory)
¹³ C-NMR (100 MHz, CDCl ₃ ): δ = 13.69 (CH ₃ ), 22.24 to 31.48 (CH ₂ ), 35.84 and 35.87 ( C H ₂ CONH and CONH C H ₂ ), 50.41 (N ⁺ (CH ₃ ) ₂ ), 62.23 (CH ₂ N ⁺ ), 64.31 (N ⁺ C H ₂ COO ^- ), 166.14 (COO ^- ), 173.93 (CONH) ppm.
MS (ESI): m / z = 365 (M ⁺ + Na, 100%).

Claims (3)

1. Process for the preparation of glycine derivatives, characterized in that the hydroxyl groups of β-hydroxyethylammonium compounds are electrochemically oxidized to give the corresponding acids.
2. Process according to Claim 1, characterized in that the aqueous solutions of β-hydroxyethylammonium compounds are electrochemically oxidized using electrodes coated with nickel oxide hydroxide to give the corresponding acids.
3. Process according to Claims 1 and 2, characterized in that the β-hydroxyethylammonium compounds are oxidized at a pH in the range from 8 to 14.