[No public or meaningful name is available]

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

other: report

Title:

Unnamed

Year:

2020

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Because of the low solubility in water, direct solution hydrolysis with water as solvent is not possible.
Hydrolysis was studies using two different solvents (THF and dioxane) and three different buffers (pH 4.2, 7 and 9). A series of hydrolyses with a biphasic system (chloroform + buffer, stirring) was also performed.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate

Cas Number:

2311845-49-3

Molecular formula:

C33H42N4O3S4

IUPAC Name:

bis(2,2,6,6-tetramethyl-1-(1,3-benzothiazol-2-ylsulfanyl)piperidin-4-yl)carbonate

Study design

Duration of test

Duration of test 1

Duration:

5 d

pH:

9

Temp.:

50 °C

Remarks:

What the effective pH in an organic solvent will be is not easily measured, it is a project in it's own right.

Duration of test 2

Duration:

5 d

pH:

7

Temp.:

50 °C

Remarks:

What the effective pH in an organic solvent will be is not easily measured, it is a project in it's own right.

Duration of test 3

Duration:

5 d

pH:

4.2

Temp.:

50 °C

Remarks:

What the effective pH in an organic solvent will be is not easily measured, it is a project in it's own right.

Results and discussion

Transformation products:

yes

Any other information on results incl. tables

Sample Abbreviation: Btz-S-Ntmp-O-CO-O-Ntmp-S-Btz

Referenz sample:
The main peak at 17 min consits of the sample. The peak at 8.5 min is interpreted as Btz-S-Ntmp-O-CO-O-Ntmp-H (note: compounds do not ionize equally well in the MS source, so peak size should not immediately be taken as a measure of concentration).

Sample in THF with 5 % buffer at pH 4.2:
The most severely decomposed sample consists mainly of the disulfide, Btz-S-S-Btz at 10 min and some Btz-S-Ntmp-O-CO-O-tmpN-H at 8.5 min. Almost all starting material at 16 min is gone.

Sample in THF with 5 % buffer at pH 7:
Sample shows less reaction, a significant amount of starting material is left (16 min). Here the predominant product is Btz-S-Ntmp-O-CO-O-tmpN-H at 8.5 min, with some Btz-S-S-Btz at 10 min also present.

Sample in THF with 5 % buffer at pH 9:
Sample shows less reaction, the product is Btz-S-Ntmp-O-CO-O-tmpN-H (8.5 min) with most of the starting material still present at 16 min.

Sample in dioxane with 5 % buffer at pH 7 & 9:
Shows a somewhat opposite behavior, with more reactivity in pH 9  than at pH 7. The product is Btz-S-Ntmp-O-CO-O-tmpN-H at 8.5 min. Rest is starting material at 16 min.

Sample in dioxane with 5 % buffer at pH 4.2:
Was not run due to solubiliy problems.

Overall:
what seems to happen in an environment with 5 % water present at 50 °C is predominantly cleavage of the S-N bond forthe sample, although the cleavage is not neccessarily homolytic. No carbonate bond cleavage was seen.

NMR runs:
NMR is not that informative in this case, as this is a reaction mixture, with quite severe congestion in the higher field range and overlapping solvent peaks. Also, the high number of heteroatoms makes long range correltation hard to find.
Nevertheless the aromatic range is rather clear, and some samples were run. Note that these samples differ from the LCMS samples in that the NMR samples were rotary evaporated at 60 °C.
If characteristic aromatic peaks from the preceding spectra (reactions in THF) are integrated, and the proportions of different benzothiazol containing compunds are calculated, the following table is obtained:

pH	Starting material [%]	Unknown compound [%]	Disulfide [%]
4.2	8	48	44
7	84	10	6
9	63	19	18

Applicant's summary and conclusion

Conclusions:

Overall, what seems to happen in an environment with 5 % water dissolved in organic solvent at 50 °C under argon is predominantly cleavage of the S-N bond, although the cleavage is not necessarily homolytic. No carbonate bond cleavage was seen.

Executive summary:

The hydrolysis of the sample was studied in-house with liquid chromatography and NMR-spectroscopy. Becausee of the low solubility in water direct solution hydrolysis with water as solvent is not possible, however, there also needs to be a salt-based buffer present. A compromise solvent mixture was used with 95 vol-% organic solvent and 5 % 10 mM sodium phosphate buffer at pH 4.2, 7 and 9.

The hydrolysis reactions were run under argon at 50 °C for five days.

Overall, what seems to happen in an environment with 5 % water dissolved in organic solvent at 50 °C under argon is predominantly cleavage of the S-N bond, although the cleavage is not necessarily homolytic. No carbonate bond cleavage was seen:
Btz-S-Ntmp-O-CO-O-Ntmp-S-Btz reacts under the above conditions mainly to Btz-S-Ntmp-O-CO-O-Ntpm-H.