Dihydro-3-[3-(triethoxysilyl)propyl]furan-2,5-dione

Hydrolysis

Description of key information

Hydrolysis half-life (furandione group): <1 hour at pH 4, 7 and 9 and 25°C (OECD 111) based on read-across from succinic anhydride (same ring structure).
Hydrolysis half-life (ethoxysilane groups): 27.6 h at pH 7, 0.7 h at pH 4, 0.7 h at pH 5, 0.4 h at pH 9 and 20-25°C (QSAR). In dilute solution, acidification is unlikely to be significant, but note that internal catalysis may be possible, therefore these half-lives should be considered maximum values.

Additional information

The substance (3-[3-(triethoxysilyl)propyl]oxolane-2,5-dione) has two types of hydrolysable group, ethoxysilane (Si-O-CH₂CH₃) and furandione (C(=O)-O-C(=O) as part of a ring). The furandione group is expected to hydrolyse rapidly or very rapidly in water, for example, in Bunton et al 1963, hydrolysis half-lives of 33.3 minutes (0.55 h) at 0°C and 4.3 minutes (0.072 h) at 25.1°C (pH not stated) were reported for succinic anhydride (CAS No. 108-30-5). The hydrolysis product is (2-[3-(triethoxysilyl)propyl]butanedioic acid) as an intermediate hydrolysis product. Subsequently, hydrolysis of the ethoxy groups would produce 2-[3-(trihydroxysilyl)propyl]butanedioic acid and ethanol.

 

The hydrolysis half-lives of the intermediate hydrolysis product, 2-[3-(triethoxysilyl)propyl]butanedioic acid have been predicted using a validated QSAR estimation method to be 0.7 h at pH 4, 0.7 h at pH 5, 27.6 h at pH 7, and 0.4 h at pH 9 and 20-25°C. There is a possibility of an internal catalysis if one of the carboxylic acid groups in the side-chain of 2-[3-(triethoxysilyl)propyl]butanedioic acid directly catalyses the Si-O hydrolysis, thus increasing the reaction rate of the ethoxy group. This effect is likely to be stronger under basic conditions when the acid groups are substantially dissociated. The half-life therefore cannot be predicted with accuracy and the stated values should be considered maximum values.

 

It is probable that the butanedioic group would complex with the calcium or other metals present in ecotoxicity test media (and potentially in some environmental waters) to form an insoluble salt which precipitates out of solution. This is consistent with findings in solubility trials performed in association with REACH-required ecotoxicity studies.

 

In a secondary source to which reliability could not be assigned, hydrolysis half-lives of 1.3 h at pH 4, 6.1 h at pH 7, 2.6 h at pH 9 were reported for the substance. There was no information on temperature stated and the products of reaction are not stated, so it is not possible to interpret which of the hydrolysable functional groups this hydrolysis rate relates to. Also, the solubility was exceeded in the test which was performed in a cosolvent system. For these reasons this experimental result cannot be interpreted for use in the chemical safety assessment.

 

Hydrolysis reactions of alkoxysilanes can be catalysed by both acid and base. The rate of hydrolysis is slowest close to pH 7 and increases as the pH is raised or lowered. For an acid-base catalysed reaction in buffered solution, the measured rate constant is a linear combination of terms describing contributions from the uncatalyzed reaction as well as catalysis by hydronium, hydroxide, and general acids or bases.

 

k_obs= k₀+ k_H3O+[H3O⁺] + k_OH-[OH^-] + k_a[acid] + k_b[base]

 

At extremes of pH and under standard hydrolysis test conditions, it is reasonable to suggest that the rate of hydrolysis is dominated by either the hydronium or hydroxide catalysed mechanism. This is supported by studies for various organosilicon compounds in which calculation of k_H3O+ and k_OH- from the experimental results at pH 4 and 9, respectively, resulted in reasonable estimates of the half-life at pH 7.

 

Therefore, at low pH:

 

k_obs≈k_H3O+[H₃O⁺]

 

At pH 4 [H₃O⁺] = 10^-4 mol dm^-3 and at pH 2 [H₃O⁺] = 10^-2 mol dm^-3; therefore, k_obs at pH 2 should be approximately 100 times greater than k_obs at pH 4.

 

The half-life of a substance at pH 2 is calculated based on:

 

t_1/2(pH 2) = t_1/2(pH 4) / 100

 

The calculated half-life of 2-[3-(triethoxysilyl)propyl]butanedioic acid at pH 2 and 20 - 25°C is therefore 0.007 hours (approximately 25 seconds).

 

Reaction rate increases with temperature therefore hydrolysis will be faster at physiologically relevant temperatures compared to standard laboratory conditions. Under ideal conditions, hydrolysis rate can be recalculated according to the equation:

 

DT₅₀(XºC) = DT₅₀(T) x e^(0.08.(T-X))

 

Where T = temperature for which data are available and X = target temperature.

 

Thus, for 2-[3-(triethoxysilyl)propyl]butanedioic acid the hydrolysis half-life at 37.5ºC and pH 7 (relevant for lungs and blood) is approximately 10 hours. At 37.5ºC and pH 2 (relevant for conditions in the stomach following oral exposure), it is not appropriate to apply any further correction for temperature and the hydrolysis half-life is therefore approximately 5 seconds. At 37.5ºC and pH 5.5 (relevant for dermal exposure), the hydrolysis half-life will be in between the half-lives at pH 5 and pH 7 at 37.5ºC (0.3 - 10 h). As the half-life at 20 - 25°C is subject to uncertainty and is a maximum half-life value, so the half-lives at elevated temperature are also maximum values.

 

The ultimate silanol product of the hydrolysis reaction under dilute conditions is 2-[3-(trihydroxysilyl) propyl]butanedioic acid. The other hydrolysis product is ethanol.