5-(N,N-diethylaminosulphonyl)-2-methoxybenzenediazonium chloride

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

November 2017

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

substance prepared in situ in acidic solution. At t0 the solution was neutralized to pH 7 and test was started

Principles of method if other than guideline:

The study was performed according to the principles described in the guideline, i.e. preliminary screening at 50°C and assessment of hydrolysis at 20°C and neutral pH. Unlike the OECD guideline, only pH 7 was tested. Moreover, due to the instability of the substance, the substance was made in situ by a diazotization reaction. The resulting acidic solution containing the newly formed diazonium salt was neutralized to pH 7 on t0 and the test was started.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-(N,N-diethylaminosulphonyl)-2-methoxybenzenediazonium chloride

EC Number:

248-543-4

EC Name:

5-(N,N-diethylaminosulphonyl)-2-methoxybenzenediazonium chloride

Cas Number:

27580-14-9

Molecular formula:

C11H16ClN3O3S

IUPAC Name:

5-(diethylsulfamoyl)-2-methoxybenzene-1-diazonium chloride

Test material form:

solid

Specific details on test material used for the study:

IN SITU SYNTHESIS OF THE DIAZONIUM SALT
3-amino-N,N-diethyl-4-methoxybenzenesulphonamide (CAS 97-35-8) was converted in a diazotisation reaction to its corresponding diazonium salt.

1) 3-amino-N,N-diethyl-4-methoxybenzenesulphonamide (20,67 g) was suspended in mixture of 25 mL water and 21.3 mL 30 % HCl at 0°C.
2) The mixture was cooled in an ice bath to 0°C and stirred for 30 min
3) A pre-cooled 30 % aq. solution of NaNO2 (80 mmol) was added dropwise over 2h to induce the diazotisation reaction. This reaction is highly exothermic and needs to be carried out carefully. The internal temperature was continuously monitored and maintained below 5°C.
4) Afterwards, the reaction mixture was diluted with water (100 mL) and stirred for another 30 minutes and kept at 0°C.
5) The products were not isolated, but kept in this aqueous solution in an ice bath. The hydrolysis experiments were immediately started.

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Remarks:

LC-UV-MS

Details on sampling:

Pre-test at 50°C:
- Sampling intervals: 5 days

Main test at 20°C:
- Sampling intervals: 0, 3, 6, 12, 24, 48, 72, 96, 120 h
- Sampling method: vials from which sample was taken were not used anymore after sampling
- Sampling intervals/times for pH measurements: pH measurement at test start
- Sampling intervals/times for sterility check: not performed
- Sample treatment: filtered in case of precipitation or diluted in 1:5 methanol
- Sample storage conditions before analysis: direct analysis

Buffers:

phosphate buffer 0.1M at pH 7

Details on test conditions:

TEST SYSTEM
- Type, material: glass test flasks and vials
- Sterilisation method: none
- Lighting: none
- Measures taken to avoid photolytic effects: incubation in the dark
- Temperature: pre-test at 50°C and main test at 20°C in thermostated oven


TEST MEDIUM
- Preparation of test medium: synthesis solution with concentration 60 mg/mL dissolved 1:30 in 0.1 M phosphate buffer of pH 7
- For main test at 20°C: synthesis solution divided over 20 separate vials
- Renewal of test solution: samples were not disturbed during hydrolysis period

OTHER TEST CONDITIONS
- Adjustment of pH: after dissolution, pH was checked

Duration of test

Duration:

120 h

pH:

7

Temp.:

20 °C

Results and discussion

Preliminary study:

Degradation after 5 days at 50°C was complete. No reference compounds were formed.

Transformation products:

yes

Identity of transformation products

Reference

Reference substance name:

Unnamed

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

Key result

pH:

7

Temp.:

20 °C

DT50:

> 5 d

Remarks on result:

other: final test

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

50 °C

DT50:

< 5 d

Remarks on result:

other: preliminary test

Details on results:

see any other information on results incl.tables

Any other information on results incl. tables

The diazonium salt was found to remain quite stable for the full 5-day duration of the hydrolysis experiment. The final concentration remains at ca. 80% of the starting concentration.

 

The formation of two minor degradation products was observed. It concerns 2-hydroxy-5-diethylsulfonylbenzenediazonium chloride, and 4-diethylsulfonylanisole. During the course of the hydrolysis experiment, their concentrations increase slowly, but none of both reach 10% after 5 days.

 

A number of other impurities were found present in the hydrolysis solution in low concentration, but none of them reaches a concentration of 2% of the parent diazonium salt.

Applicant's summary and conclusion

Validity criteria fulfilled:

not applicable

Conclusions:

The 5-(N,N-Diethylaminosulphonyl)-2-methoxybenzenediazonium chloride was found to be stable in the aqueous phase. Minimal degradation is observed and ca. 80% of the starting concentration remains after 120h at 20°C.

Executive summary:

The hydrolysis of the diazonium salt 5-(N,N-Diethylaminosulphonyl)-2-methoxybenzenediazonium chloride was investigated in a study based on the principles of OECD 111. Deviation compared to the guideline was needed since the diazonium salt had to be generated in situ due to it's reactivity and explosive properties when isolated.

First, 3-amino-N,N-diethyl-4-methoxybenzenesulphonamide (CAS 97-35-8) was converted in a diazotisation reaction to its corresponding diazonium salt, 5-(N,N-Diethylaminosulphonyl)-2-methoxybenzenediazonium chloride. This acidic cooled solution was neutralised to pH 7 in a phosphate buffer. This was considered to be t0 of the experiment.

In the main study at 20°C, the hydrolysis was followed by sampling after 0, 3, 6, 12, 24, 48, 72, 96 and 120h. Samples were filtered or diluted in methanol (1:5) and directly measured by LC-UV-MS. This analysis allowed a semi-quantitative analysis of the degradation products.

In the pre-test conducted at 50°C, the diazonium salt was found to degrade. Unexpectedly, the diazonium salt was found to remain quite stable for the full 5-day duration of the hydrolysis experiment at 20°C and pH 7. At 20°C after 120h, the concentration of diazonium salt

remained ca. 80 % of the starting concentration. The formation of two minor degradation products was observed. It concerns 2-hydroxy-5-diethylsulfonylbenzenediazonium chloride, and 4-diethylsulfonylanisole. During the course of the hydrolysis experiment, their concentrations increase slowly, but none of both reach 10% after 5 days.