4-(2-chlorophenyl)-N-cyclohexyl-N-ethyl-5-oxo-4,5-dihydro-1H-tetrazole-1-carboxamide

Melting point / freezing point

Link to relevant study record(s)

Reference

Endpoint:

melting point/freezing point

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Sep - 5 Nov 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 102 (Melting point / Melting Range)

GLP compliance:

yes

Type of method:

differential scanning calorimetry

Melting / freezing pt.:

>= 78.7 - <= 79.7 °C

Atm. press.:

ca. 1 013 hPa

Decomposition:

yes

Decomp. temp.:

235 °C

Screening experiment:

Temperature program: 25 °C — > 320 °C (20 K/Min), aluminum crucible with perforated lid. The screening curves of all samples investigated are similar.

The following table gives individual results, averages and relative standard deviations for the endothermic and exothermic peaks for all batches.

batch	endo				exo
	AH	onset	Peak	Peak width	AH	onset	Peak	Peak width
	[J/g]	[°C]	[°C]	[°C]	[J/g]	[°C]	[°C]	[°C]
960110ELB01	-80.57	80.54	84.61	5.33	411.55	235.24	255.31	18.85
898443001	-81 .26	79.57	82.73	3.5	595.69	231.35	255.46	23.92
898443002	-86.16	80.4	84.41	5.53	445.05	234.85	255.37	20.59
898443003	-84.26	80.14	84.43	5.59	470.81	232.92	255.41	22.14
898443004	-80.91	79.44	83.47	5.35	451.66	235.4	255.96	19.51
898443005	-81 .32	79.79	83.72	5.29	410.09	235.59	256	19.63
898443006	-79.46	79.69	83.19	4.38	379.15	235.82	256.37	19.86
898443007	-81.6	79.86	84.46	7.16	456.93	236.82	257.27	17.21
average	-81.94	79.93	83.88	5.27	452.62	234.75	255.89	20.21
rsd [%]	-2.66	0.49	0.84	19.89	14.41	0.75	0.26	10.14

In the following table individual results for all batches of first the experiment and the averages and relative standard deviations for both experiments (2 K/min and 0.6 K/min) are given:

batch	sample weight	purity	Tf	Tf, pure	DeltaHFusion	Corr. factor
	[mg]	[Mol-%]	[°C]	[°C]	[J/g]	[%]
960110ELB01	6.10	98.771	79.68	80.12	84.22	14.48
898 443 001	6.40	99.129	79.02	79.36	73.97	9.17
898 443 002	5.90	99.423	79.38	79.59	83.97	7.73
898 443 003	7.07	98.933	79.69	80.05	87.98	12.08
898 443 004	3.49	99.122	78.75	79.06	82.97	9.50
898 443 005	3.96	99.092	78.91	79.24	81.39	9.82
898 443 006	7.03	98.974	79.03	79.39	82.41	9.02
898 443 007	6.01	99.034	78.70	79.05	81.41	8.79
average	5.75	99.060	79.15	79.48	82.29	10.07
rsd [%]	23.10	0.190	0.50	0.52	4.82	21.52
0.6 K/Min
average	7.55	99.144	78.62	78.92	83.38	11.63
rsd [%]	43.47	0.225	0.30	0.26	3.34	15.55

The melting points and enthalpies of fusion show relatively high standard deviations and there is a significant difference depending on the rate of heating. The melting enthalpies found in the experiment with 2 K/min ( ΔH_F 82.3 J/g + 4.8 %) are a little less but comparable to those found in the screening experiment ( ΔH_F 83.9 J/g ± 0.8 %) using a faster heating (20K/min) and the second experiment for purity determination using a lower heating ramp yields ΔH_F close to the value from screening.

Batches 898 443 001 and 898 443 007 were measured three times at 2 K/min. Individual results of the additional runs, averages of the three results for these two batches, and relative standard deviations are given in the following table:

batch	sample weight	purity	Tf	Tf, pure	DeltaHFusion	Corr. factor
	[mg]	[Mol-%]	[°C]	[°C]	[J/g]	[%]
898 443 001	2.74	99.369	78.46	78.7	77.12	7.48
898 443 001	3.73	99.225	78.67	78.96	77.35	9.69
898 443 007	6.16	99.204	78.57	78.87	78.15	8.23
898 443 007	7.29	99.07	79.06	79.46	67.4	8.27
average of 3
898 443 001	4.29	99.24	78.72	79.01	76.15	8.78
rsd [%]	44.13	0.12	0.36	0.42	2.48	13.16
898 443 007	6.91	99.11	78.90	79.26	70.98	8.26
rsd [%]	10.12	0.09	0.32	0.38	10.33	3.78

Three experiments were carried out:

1.) Batch 898 443 001 (6.87 mg, sealed aluminum crucible) with the following temperature program:

Segment	start temperature [°C]	ramp [K/min]	end temperature [°C]
1,4,7,10	62	0.5	82
2,5,8, 11	82	-5	0
3,6,9,12	0	5	62

In the first segment melting is observed (Tf 78.17 °C, Purity 99.045 mol%, AH 77.09 J/g) but recrystallization and remelting is not observed. A glass transition is found in the heating segments 3, 6, 9, and 12: midpoint 5.28, 5.13, 3.06, and 3.45 °C, average: 4.2 ± 1.1 °C

2.) Batch 898 443 001 (7.03 mg, sealed aluminum crucible) with the following temperature program:

Segment	start temperature [°C]	ramp [K/min]	end temperature [°C]
1	25	10	60
2, 5, 8,	60	2	82
3, 6, 9,	82	-10	-10
4,7,10,	-10	10	60

Virtually the same curves are obtained. Melting occurs in the second segment (Tf 79.09 °C, purity 99.130 mol%, AH 76.82 J/g) and the glass transition is observed upon heating at the same temperature (midpoint 3.3 ± 0.02 °C).

 

3.) a sample of batch 898 443 001 was recrystallized from 2-propanol and dried in vacuo (0.18 % 2-propanol according to headspace GC in the sample). Temperature program as in 1.

Again virtually the same curves are obtained. Melting occurs in the first segment (Tf 78.33 °C, purity 99.51 mol%, AH 81.15 J/g) and the glass transition is observed upon heating at slightly higher temperature (midpoint 5.6 ±0.15 °C).

TGA:

The first decomposition step corresponds to loss of a fragment with mass ~ 349.9 x 0.99 x 0.5684 = 197 (molecular weight of YRC 2388 x purity x step height). Kinetic evaluation of the SDTA (= Single Differential Thermal Analysis, comparable to DSC, but less accurate) peak, gives n = 1.05, EA = 199 kJ/mol, and In(kO) = 41 in very good agreement with the above result from screening DSC.

The melting point is found to be very sensitive to measuring conditions.

There is no indication from either differential scanning experiments nor from infrared spectra that a second crystalline modification is present. From a more polar solvent the same crystalline modification precipitates.

There are strong indications of some amorphous portions in the precipitated samples, as the enthalpies of fusion vary more than usual. Recrystallization of the substance could not be achieved. The melt solidifies as a glass with a glass transition temperature at approximately 5 °C.

From DSC and TGA analysis a remarkable thermostability of the substance is inferred. The decomposition starts with onset temperature 235 °C (at 20 K/min heating rate). The first decomposition step corresponds to a defined chemical reaction.

The melting point of substance depends on the measuring conditions and for the pure substance the range is: 78.7 - 79.7 °C from the experiments reported here.

The test substance is stable in the melt and decomposition is slow up to a temperature of above 200°C.

From the melt no recrystallization could be achieved, the product solidifies as a glassy melt with a glass transition around 5 °C. The samples seem not to be completely crystalline but to contain some amorphous portions (as estimated from the enthalpies of fusion). A sample crystallized from 2-propanol (a solvent not used in the technical process) has the same melting point as the starting material.

No indications were as yet found of a metastable crystal modification.

Description of key information

Melting range = 78.7-79.7 °C at ca. 1013 hPa (OECD Guideline 102, differential scanning calorimetry)

Additional information

Decomposition observed starting at 235 °C.