Trisodium dicarboxymethyl alaninate

The patent literature on the industrial synthesis of trisodium N-(1-carboxylatoethyl)iminodiacetate describes the approaches for solving the key requirements of a manufacturing process that can be implemented on an industrial scale, characterized by

• Achieving the highest possible space-time yields
• Simple reaction control at relatively low pressures and temperatures
• Realization of continuous process options
• Achieving the lowest possible levels of impurities, particularly nitrilotriacetic acid, which is suspected of being carcinogenic
• Use of inexpensive raw materials, e.g. instead of pure L-alanine the raw mixture of Strecker synthesis from methanal, hydrogen cyanide and ammonia
• Avoidance of complex and yield-reducing isolation steps; instead, direct further use of the crude reaction solutions or precipitates in the following process step.

An obvious synthesis route to α-alaninediacetic acid is from racemic α-DL-alanine, which provides racemic α-ADA by double cyanomethylation with methanal and hydrogen cyanide, hydrolysis of the intermediately formed diacetonitrile to the trisodium salt and subsequent acidification with mineral acids in a 97.4% overall yield.^[4] In a later patent specification, however, only an overall yield of 77% and an NTA content of 0.1% is achieved with practically the same quantities of substances and under practically identical reaction conditions.^[5]

This later patent specification^[5] also indicates a process route via alaninonitrile, which is obtained by Strecker synthesis from hydrogen cyanide, ammonia and methanal and converted to methylglycinonitrile-N,N-diacetonitrile by double cyanomethylation (step 1). The three nitrile groups are then hydrolyzed with sodium hydroxide to α-ADA (step 2). The total yield is given as 72%, the NTA content as 0.07%.

One variant of the reaction involves iminodiacetonitrile or iminodiacetic acid (step 1'), which reacts in a weakly acidic medium (pH 6) with hydrogen cyanide and ethanal to form methylglycinonitrile-N,N-diacetic acid, the nitrile group of which is hydrolyzed with sodium hydroxide to trisodium N-(1-carboxylatoethyl)iminodiacetate (step 2'). The reactant iminodiacetic acid is accessible at low cost by dehydrogenation of diethanolamine. Again, the total yield is given as 72%, the NTA content as 0.07%.

A further variant is suitable for continuous production, in which ammonia, methanal and hydrogen cyanide react at pH 6 to form iminodiacetonitrile, which in a strongly acidic medium (pH 1.5) reacts with ethanal to produce trinitrile methylglycinonitrile-N,N-diacetonitrile in a very good yield of 92%. (step 1).

Alkaline hydrolysis (step 2) results in a total yield of 85% trisodium N-(1-carboxylatoethyl)iminodiacetate with an NTA content of 0.08%. This process variant seems to fulfil the above-mentioned criteria best.

A low by-product synthesis route for trisodium N-(1-carboxylatoethyl)iminodiacetate has recently been described, in which alanine is ethoxylated with ethylene oxide in an autoclave to form bis-hydroxyethylaminoalanine and then oxidized to α-ADA at 190 °C with Raney copper under pressure.^[6]

The yields are over 90% d.Th., the NTA contents below 1%. The process conditions make this variant rather less attractive.

The commercially available trisodium N-(1-carboxylatoethyl)iminodiacetate (84% by weight) is a colourless, water-soluble solid whose aqueous solutions are rapidly and completely degraded even by non-adapted bacteria. Aquatic toxicity to fish, daphnia and algae is low.^[7] Trisodium N-(1-carboxylatoethyl)iminodiacetate is described as readily biodegradable (OECD 301C) and is eliminated to >90 % in wastewater treatment plants.^[8] Trisodium N-(1-carboxylatoethyl)iminodiacetate has not yet been detected in the discharge of municipal and industrial sewage treatment plants. In addition to their very good biodegradability, trisodium N-(1-carboxylatoethyl)iminodiacetate solutions are characterized by high chemical stability even at temperatures above 200 °C (under pressure) in a wide pH range between 2 and 14 as well as high complex stability compared to other complexing agents of the aminopolycarboxylate type.^[1][9]

The following table shows the complexing constants log K of α-ADA compared to tetrasodium iminodisuccinate and ethylenediaminetetraacetic acid (EDTA) versus polyvalent metal ions:

The complex formation constants of the biodegradable chelators α-ADA and IDS are in a range suitable for industrial use, but clearly below those of the previous standard EDTA.

In solid preparations, trisodium N-(1-carboxylatoethyl)iminodiacetate is stable against oxidizing agents such as perborates and percarbonates, but not against oxidizing acids or sodium hypochlorite.

Like other complexing agents in the aminopolycarboxylic acid class, trisodium N-(1-carboxylatoethyl)iminodiacetate (α-ADA) finds due to its ability to form stable chelate complexes with polyvalent ions (in particular the water hardening agents Ca²⁺ and Mg²⁺, as well as transition and heavy metal ions such as Fe³⁺, Mn²⁺, Cu²⁺, etc.) use in water softening, in detergents and cleaning agents, in electroplating, cosmetics, paper and textile production. Due to its stability at high temperatures and pH values, α-ADA should be particularly suitable as a substitute for the phosphates banned in the EU from 2017, such as sodium tripolyphosphate (STPP)^[12] in tabs for dishwashers.

BASF SE is the most important manufacturer of α-ADA under the brand name Trilon M, has large-scale plants in Ludwigshafen and Lima, Ohio, and is currently expanding its existing capacities with another large-scale plant at Evonik's site in Theodore, Alabama.^[13]