N -methyliminodiacetic acid

Structural formula
General
Surname	N -methyliminodiacetic acid
other names	N - (carboxymethyl) - N -methylglycine 2- [carboxymethyl (methyl) amino] acetic acid MIDA
Molecular formula	C 5 H 9 N 2 O 4
Brief description	colorless crystalline solid
External identifiers / databases
CAS number 4408-64-4 EC number 224-557-6 ECHA InfoCard 100.022.326 PubChem 20441 ChemSpider 19251 Wikidata Q55718181
properties
Molar mass	147.13 g mol −1
Physical state	firmly
Melting point	220 ° C with decomposition 223–225 ° C with decomposition 226–227 ° C with decomposition
solubility	Easily soluble in water, poorly soluble in dimethyl sulfoxide , practically insoluble in ethanol and diethyl ether
safety instructions
GHS labeling of hazardous substances Caution H and P phrases H: 315-319-335 P: 261-305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

N -Methyliminodiacetic acid is a tridentate complexing agent , the chelate complexes with cations with a charge number of at least +2, z. B. the "water hardness builders" forms Ca ²⁺ or Mg ²⁺ . As a MIDA protective group in boric acid esters , the so-called Burke boronates , N - (carboxymethyl) - N -methylglycine plays an important role z. B. in Suzuki-Miyaura couplings .

Manufacturing

The preparation of N -methyliminodiacetic acid was described as early as 1894 by Wilhelm Eschweiler from methylamine and glycolonitrile (here called "methylene cyanohydrin").

MIDA (called here "methyldiglycolamic acid") is obtained after hydrolysis of the N -methyliminodiacetonitrile "in well-developed, colorless columns."

The reaction of methylamine with monochloroacetic acid gives MIDA in 63 to 71% yield.

When iminodiacetic acid IDA is reacted with a mixture of formic acid and formaldehyde , N- methyliminodiacetic acid is produced in 83% yield.

A detailed process description for this Eschweiler-Clarke methylation has recently been published, according to which MIDA is obtained as a white powder in 88% yield.

Since iminodiacetic acid is available in large quantities as a key raw material in two standard processes for the production of the herbicide glyphosate , this route should currently make the most economic sense.

properties

N -methyliminodiacetic acid is a solid which is obtained as a white crystal powder and is readily soluble in water, but only slightly or practically insoluble in dimethyl sulfoxide and ethanol. For cleaning, the substance can be dissolved in warm water and precipitated by adding methanol .

Applications

The significantly lower complex formation constants of N -methyliminodiacetic acid compared to polyvalent metal ions compared to standard compounds, such as. B. Nitrilotriacetic acid NTA, (for Ca ²⁺ 3.75 versus 6.41 for NTA) make MIDA uninteresting as a complexing agent for technical applications.

In contrast, N -methyliminodiacetic acid has gained considerable importance in recent years as a protective group in functional boric acid esters, the so-called MIDA boronates or - according to the author of the first publication, Martin D. Burke - “Burke boronates”.

MIDA boronates are easily accessible, easy to handle, stable in air and at room temperature with dilute bases, such as. B. with one molar sodium hydroxide solution , cleavable into the corresponding boric acids.

They have proven to be valuable reagents because of the particular robustness of MIDA boronates (in contrast to many sensitive functional boron acids), their good solubility in various organic solvents and, in particular, their property of slow release of the synthetically active boron acids in the presence of mild bases, such as e.g. . B. potassium phosphate K ₃ PO ₄ , in the Suzuki-Miyaura coupling, and the suitability for iterative cross-couplings.

A large number of MIDA boronates with aromatic ( A ), heteroaromatic ( B ) or vinyl ( C ) substituents have been described and are commercially available (see examples).

Individual evidence

1. ↑ ^{a b c} I. Dailey, MD Burke: N - (carboxymethyl) - N -methyl-glycine . In: e-EROS Encyclopedia of Reagents for Organic Synthesis . 2010, doi : 10.1002 / 047084289X.rn01228 .
2. ↑ ^{a b c} data sheet methyliminodiacetic acid, 99% from Sigma-Aldrich , accessed on July 16, 2018 ( PDF ).
3. ↑ ^{a b c} A. Eschweiler: About some acetonitriles . In: Justus Liebigs Ann. Chem. Band 278 , no. 2 , 1894, p. 229-239 , doi : 10.1002 / jlac.18942780207 .
4. ↑ MIDA Boronates. In: Sigma-Aldrich, Chemical Synthesis. Sigma-Aldrich, accessed July 18, 2018 . 
5. ↑ ^{a b} G.J. Berchet: Methyliminodiacetic acid In: Organic Syntheses . 18, 1938, p. 56, doi : 10.15227 / orgsyn.018.0056 ; Coll. Vol. 2, 1943, p. 397 ( PDF ).
6. ^ AF Childs et al .: Amines containing 2-halogenoethyl groups . In: J. Chem. Soc. 1948, p. 2174-2177 , doi : 10.1039 / JR9480002174 .
7. ↑ ^{a b} S.G. Ballmer, EP Gillis, MD Burke: B-protected haloboronic acids for iterative cross-coupling In: Organic Syntheses . 86, 2009, pp. 344-359, doi : 10.15227 / orgsyn.086.0344 ( PDF ).
8. ↑ G. Schwarzenbach, G. Anderegg, W. Schneider, H. Senn: Complexone XXVI. About the coordination tendency of N-substituted iminodiacetic acids . In: Helv. Chim. Acta . tape 38 , no. 5 , 1955, pp. 1147–1170 , doi : 10.1002 / hlca.19550380509 .
9. ^ EP Gillis, MD Burke: A Simple and Modular Strategy for Small Molecule Synthesis: Iterative Suzuki-Miyaura Coupling of B-Protected Haloboronic Acid Building Blocks . In: J. Am. Chem. Soc. tape 129 , no. 21 , 2008, p. 6716–6717 , doi : 10.1021 / ja0716204 .
10. ↑ Iterative Cross-Coupling with MIDA Boronates: towards a General Strategy for Small-Molecule Synthesis. In: Aldrichimica Acta, 42 (1), pp. 17-29. Sigma-Aldrich, 2009, accessed July 18, 2018 .