Do the amino groups in EDTA deprotonate first, in contrast to amino acids?

We know that in amino acids, carboxylic acid groups deprotonate first than the amine groups. For example, in alanine, $\mathrm

K_\mathrm> = 2.34$, $\mathrm

K_\mathrm> = 9.69$ according to this page. But according to the structures of EDTA as searched from Google, and from this extract from p.325 of Analytical Chemistry, 8e by Christian, et al.:

At sufficiently low pH, the nitrogens can also be protonated and this diprotonated EDTA can be considered a hexaprotic acid. However, this occurs at a very low pH and EDTA is almost never used under such conditions.

the hydrogens of these amino groups seem to be deprotonated first before those of the four carboxylic acid groups. Why is this so?

41.5k 8 8 gold badges 74 74 silver badges 192 192 bronze badges asked Nov 21, 2017 at 3:38 819 1 1 gold badge 7 7 silver badges 14 14 bronze badges $\begingroup$ Before you ask "why", ask "if". $\endgroup$ Commented Nov 21, 2017 at 5:14 $\begingroup$ How many covalent bonds can N form with other elements? $\endgroup$ Commented Nov 21, 2017 at 8:33

$\begingroup$ There used to be a place on the internet where you could enter compounds and things such as acidity constants were calculated, including which proton deprotonated in which order. Alas, I can’t find the site any more. $\endgroup$

Commented Nov 21, 2017 at 14:31

$\begingroup$ I mean you should not blindly trust some random images brought to you by Google image search. Trust your logic; it is sound. $\endgroup$

Commented Nov 24, 2017 at 12:02

$\begingroup$ @IvanNeretin, okay, I added another reference that supports this ionization behavior of EDTA. $\endgroup$

Commented Nov 25, 2017 at 3:24

2 Answers 2

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Dissolved in water, EDTA can have net charges varying from -4 to +2, from fully deprotonated to all four carboxylic acid groups and two amine groups protonated.

It is the fully deprotonated form that binds to divalent cations (see e.g. https://chemistry.stackexchange.com/a/81988/72973). If necessary, deprotonation occurs upon binding (see e.g. https://doi.org/10.1016/S0301-4622(99)00047-2).

The intermediate protonation states occur as zwitterions both in aqueous solution and in some of the crystal forms. Disodium EDTA is an example:

enter image description here

[OP] the hydrogens of these amino groups seem to be deprotonated first before those of the four carboxylic acid groups. Why is this so?

In aqueous solution, this carboxylic acid deprotonates before the ammonium. If you see other statements, they ignored to mention the prevalent tautomeric state. The situation in organic solvents might be different. The neutral species might have the carboxylic acid groups protonated and the amines deprotonated when EDTA is dissolved in a no-ionic organic solvent. The cationic or anionic species would probably not be soluble, so for those species, the question is moot.