1,3-propanesultone

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A full test according to OECD 111 with fixed pH-values was performed. Unfortunately, it is not possible to fix the pH-values by buffering over the test time because as soon as the substance is mixed with the test water the pH decreases extremly. This pH-shift is likely due to hydrolysis of 1,3-propanesultone forming hydroxypropansulfonic acid, CAS 15909-83-8 due to hydrolytically induced ring cleavage. The preliminary results from the cancelled OECD 111 test are given below.Although unexpected problems occured and the study had to be cancelled the preliminary results are in line with theoretical assumptions on the hydrolysis of the substance. Hence, the results can be used to assess the hydrolytical stability of 1,3-propanesultone.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes

Radiolabelling:

no

Analytical monitoring:

yes

Buffers:

- pH 4: (Bern Kraft; Citric acid, sodium chloride, sodium hydroxide)
-pH 7: (Bern Kraft;phosphate mixture)
-pH 9. (Pre-testBern Kraft; boric acid, potassium chloride, sodium hydroxide); tiethylamine hydrochloride, tris(hydrolxymethyl)aminomethande

Positive controls:

no

Negative controls:

no

Preliminary study:

Pre-Test at 50°C:
The test item was completely hydrolysed at t1/2 <2 (estimated) at pH4, pH7 and pH 9

Test performance:

0.52 - 0.63 g (pre-test: 1.03 - 1.37 g) of the test item exactly
weighed were dissolved in 50 ml (pre-test: 100 ml) of buffer
pH 4 or pH 9 (pre-test: buffer pH 4, pH 7 or pH 9). The buffer
solutions were fumigated with nitrogen prior to the application.
Considering the molar mass of the test item with 122.14 g/mol,
the concentrations of test item in the resulting solutions
correspond to - 0.1 mol/1.
Individual results
Test
pH 4 (3.7 -1.6)*
pH 7 (6.5 - 2.9)*
pH 9 (8.5 - 3.5)*
pH 4 (4.0 - 1.9)*
pH 4 (4.0- 1.9)*
pH 9 (8.8 - 1.3)*
pH value
pH4
pH 7
pH 9
T
[OC]
The buffer solutions of the pre-tests at 50°C were analyzed
immediately and after approx. 4h of storage. The absorbance
found analyzing the buffer solutions after storage was below
the limit of detection (corresponds to < 10 % of the start
concentration of the test item). The further tests were carried
out using a tempered CaFrcuvette and the I R signal at
1338 cm-1 was measured continuously by IR spectroscopy with
transmittance.

Details on hydrolysis and appearance of transformation product(s):

- Formation and decline of each transformation product during test: CAS 15909-83-8, 3-hydroxy-1-propanesulfonic acid is supposed to be the product of hydrolysis due to hydrolytic ring cleavage of the parent compound. The product of hydrolysis is supposed to be hydrolytically stable as it does no contain labile functional groups.
- Pathways for transformation: hydrolytic ring cleavage of the parent compound

pH:

9

Temp.:

21.3 °C

DT50:

27.7 h

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Decrease of pH from 8.8 to 1.3 at the end of the test. Hence, is is assumed that the DT50 would be lower if the pH value of 4 could have been fixed for the whole test period.

Details on results:

TEST CONDITIONS
- pH, sterility, temperature, and other experimental conditions maintained throughout the study: No
- Anomalies or problems encountered (if yes): Due to the hydrolytic ring cleavage of the parent compound 1,3-propanesultone and the subsequent formation of 3-hydroxy-1-propansulfonic acid the pH decreased rapidly in all test solutions. No buffer was found strong enough to maintain a constant pH-value over the test period (tested for pH4, pH7 and pH9).

The pH shift in the test solutions might also indicate the speed of hydrolysis. At pH 7 the whole buffer was converted after approx. 20 hours while at pH 9 the buffer was converted after approx. 150 minutes. As both test solutions contained comparable amounts of buffer and test substance it can be concluded, that the substance was fully hydrolysed after these times.

 

pH value	Tempeature [°C]	T1/2 [h]
pH 4 (4.0 – 1.9)*	19.4	(about 29)
pH 4 (4.0 – 1.9)*	30.3	(about 5)
pH 9 (8.80 – 1.3)*	21.3	(about 28)

*first value in brackets measured at test start, second values measured at test end

The decrease of the pH to lower pH values was investigated more precisely. Therefore two mixtures with approx.0.9 g of test item in 75 ml of buffer (pH 7 and pH 9) were made.

 

pH 7		pH 9
time [min]	pH	time [min]	pH
0	6.94	0	8.92
5	6.90	5	8.84
10	6.86	10	8.75
15	6.80	15	8.65
20	6.74	20	8.50
30	6.60	30	8.38
40	6.46	40	8.17
50	6.35	50	8.09
60	6.23	60	8.00
90	5.93	90	7.60
120	5.72	120	6.71
180	5.22	150	2.71
210	5.04	180	2.17
240	4.86	210	2.11
270	4.68	240	2.04
300	4.53	270	1.95
330	4.38	1020	1.40
360	4.24
390	.409
1230	2.20
1260	2.16

 

Due to the remarkable differences of the pH each measured between start and end of every test, further investigations as reported above and calculations therefrom were not sensible and therefore omitted. So the half-lives for 20°C and 25°C cannot be calculated.

Executive summary:

1,3 -propanesultone hydrolyses rapidly forming the strong acid 3 -hydroxy-1-propanesulfonic acid which leads to a strong pH-shift in the test solution.

Reference 2

Endpoint:

hydrolysis

Type of information:

other: Expert statement

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Principles of method if other than guideline:

Expert statement

Transformation products:

not measured

Remarks on result:

other: expert statement: rapid hydrolysis

A hydrolysis study is available. The study indicated that 1,3-propopanesultone is hydrolytically instable and decomposed to the 3-hydroxypropanesulfonic acid as hydrolysis product. In the Tier I study, the parent substance was not detectable after approx. 4 hours respectively at 50 °C under pH 4, 7 and 9. The Tier 2 study was conducted in the pH 4 buffer at two temperatures (20 °C and 30°C) and in the pH 9 buffer at one temperature (20°C).

3-hydroxypropanesulfonic acid is a strong acid, which acidity excessed the buffering capacity of neutral basic buffers used in the study. An additional pH declination test indicated that pH values of the buffers dropped down one hour later and up to 2 at approx. after 20 hours (pH 7) and 2.5 hours (pH 9).  For this reason, the hydrolysis rate and hydrolytic half-lives set out below were estimated based on assuming of a first-order reaction and ignoring pH decline. The results were suggested for informative purpose only.

Test*	Temp. (°C)	kobs(h^-1)	kobsMean (h^-1)	t1/2(h)	t1/2mean (h)
pH 4 (4.0 – 1.9)	19.4	0.0240519	-	approx. 29
pH 4 (4.0 – 1.9)	30.3	0.1316376	-	approx. 5
pH 9 (8.8 – 1.3)	21.3	0.0250349	-	approx. 28

*the values in brackets referred to the measured pH values at the start and the end of the tests.

Mori (1971) studied the mechanism and reactivity of hydrolysis of aliphatic sulfonate esters and five- and six membered sultones, including 1,4-butanesultone, as well as a linear sultone. The kinetic constants of a previous study (Mori, 1971b) with 1,3-Propoanesultone and 1,4-butanesultone in water at pH 7 and ionic strength of 0.5 were reported as set out in the table below:

Test substance	K1x 10^7(sec^-1)	Ea(Kcal/mol)	ΔS^≠
1,3-Propoanesultone	215	20.4±.01*	-13.8* (at 40°C)
1,4-butanesultone	5.67	20.0	- 20.0

*Bordwell (1959)

It is showed that the ration of relative reaction rates of the five-membered and 6-membered sultones in water at pH 7 is 37:1, implied the relative rate via B_AL1-E1 mechanism, as the relationship between logK₁and pH was consistent, and Ea values were the same.

Consequently, the study demonstrates that the hydrolysis of aliphatic sulfonate esters proceeded substantially by B_AL1-E1 reaction via cleavage of C-O bond, the contribution aliphatic ring structure to the reactivity is very low, and the reactivity seemed to be controlled essentially by the entropy term (ΔS^≠). The hydrolysis kinetic study indicated that the first-order reaction took place in water, but in a mixture system consisting of an aprotic solvent and water (65% of acetone-35% water), a sharp increase of hydrolytic rate was observed at pH > 7, this implied that an S_N2_E2 reaction occurring in an extent way, although the B_AL1-E1 reaction predominated.

In conclusion, 1,3-propoanesultone is considered to undergo rapid hydrolysis in water, forming the strong acid 3-hydroxypropanesulfonic acid. Predictably, the hydrolysis in water follows a first-order reaction and proceeds substantially by BAL1-E1 reaction via cleavage of C-O bond.

Reference:

Mori, A.; Nagayama, M.; Mandai, H. (1971a).Bul. Chem. Soc. Japan, 44(6):1669-1672

Mori, A.; Nagayama, M.; Mandai, H. (1971a).ibid., 74, 715

Bordwell, F.G.; Osborne, C.E.; Chapman R.D.; (1959) J. Amer. Chem. Soc., 81, 2698

Description of key information

1,3-propanesultone hydrolyses rapidly under environmental conditions.

Additional information

1,3-Propanesultone is considered to undergo rapidly hydrolysis in water, forming the strong acid 3-hydroxypropanesulfonic acid. Predictably, the hydrolysis in water follows a firs-order reaction and proceeds substantially by BAL1-E1 reaction via cleavage of C-O bond. The available guideline study according to OECD 111 indicated that 1,3-propanesultone hydrolyses rapidly forming the strong acid

, 3-hydroxypropanesulfonic acid which leads to a strong pH-shift in the test solution.