Thermophysical study of several barbituric acid derivatives by differential scanning calorimetry (DSC)

Article abstract of DOI:10.1021/je1008944

The present study reports a differential scanning calorimetry (DSC) study of the barbituric acid derivatives: 1,3-dimethylbarbituric acid [CAS 769-42-6], 5,5-dimethylbarbituric acid [CAS 24448-94-0], 1,3-diethylbarbituric acid [CAS 32479-73-5], 1,3,5-trimethylbarbituric acid [CAS 7358-61-4], 1,5,5-trimethylbarbituric acid [CAS 702-47-6], and tetramethylbarbituric acid [CAS 13566-66-0] in the temperature interval from T = 268 K to their respective melting temperatures. Temperatures, enthalpies and entropies of fusion, and the heat capacities of the solid compounds as a function of temperature are reported.

Full text of DOI:10.1021/je1008944

J. Chem. Eng. Data 2011, 56, 263–268
263
Thermophysical Study of Several Barbituric Acid Derivatives by Differential
Scanning Calorimetry (DSC)
†
,‡
,†
§
†
|
Manuel Temprado, Mar ´ı a Victoria Roux,* Francisco Ros, Rafael Notario, Marta Segura, and
James S. Chickos⊥
Institute of Physical Chemistry “Rocasolano”, CSIC, Serrano 119, 28006 Madrid, Spain, Institute of Medical Chemistry, CSIC,
Juan de la Cierva 3, 28006 Madrid, Spain, PerkinElmer Espa n˜ a S.L., Ronda de Poniente 19, 28760 Tres Cantos, Madrid, Spain,
and Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis,
Missouri 63121-4499, United States
The present study reports a differential scanning calorimetry (DSC) study of the barbituric acid derivatives:
1
,3-dimethylbarbituric acid [CAS 769-42-6], 5,5-dimethylbarbituric acid [CAS 24448-94-0], 1,3-diethyl-
barbituric acid [CAS 32479-73-5], 1,3,5-trimethylbarbituric acid [CAS 7358-61-4], 1,5,5-trimethylbarbituric
acid [CAS 702-47-6], and tetramethylbarbituric acid [CAS 13566-66-0] in the temperature interval from T
)
268 K to their respective melting temperatures. Temperatures, enthalpies and entropies of fusion, and the
heat capacities of the solid compounds as a function of temperature are reported.
Introduction
methods use a second-order additivity scheme that also take
into account nearest-neighbor interactions in the definition of
Barbituric acid derivatives were introduced for medical use
24
the structural units of molecules. These schemes normally
1
a century ago, several years after the synthesis in 1864 by von
neglect all next-to-nearest neighbor interactions because of the
limited accuracy of the available experimental heat capacity data.
Estimations of the heat capacity of solids are more problematic
than their liquid counterparts. This is due in part to the lack of
data but also due to the anisotropic nature of the solid state.
Phase transitions in solids can affect their heat capacities near
these transitions. Solids that form liquid crystals, for example,
seem to have larger heat capacities in certain temperature
regions, and phase change entropies appear attenuated in
2
Baeyer of the parent compound, barbituric acid. Barbiturates
act as central nervous system depressants, and by virtue of this,
they produce a wide spectrum of physiological effects. They
are used as sedatives, hypnotics, soporifics, anticonvulsants, or
3
adjuncts in anesthesia. Other applications of barbituric acid
4
derivatives include their use as antivirals, in photochemical
5
6
7
8
nanoscience, as dyes, polymers, dental materials, water-
9
10
thinned or oil-based inks, and as polymerization catalysts.
In the context of a systematic study of the thermodynamic
properties of this family of compounds, we have recently
25
comparison to systems that melt directly to isotropic liquids.
Group values for estimating the heat capacity of crystalline
solids have been reported, but the estimations in many cases
have been hampered by the lack of sufficient data.
During the past few years, we have been involved in the
experimental determination of enthalpies of fusion, heat capaci-
1
1
published thermochemical studies of barbituric acid and its
1
2
13
5
,5-dimethyl and 5,5-diethyl (barbital) derivatives. Ther-
mophysical data existing in the literature for these types of
compounds are scarce. Only experimental data concerning the
1
4,15
13
C
p
of barbituric acid
and the 5,5-diethyl derivative are
ties, and the study of polymorphism of pure crystalline organic
available.
26-32
compounds.
The present work reports the temperature,
Heat capacities at T ) 298.15 K have proven quite useful in
adjusting vaporization, sublimation, and fusion enthalpies with
temperature. Equations for doing this have recently been
reported by Chickos and co-workers.
compilations of critically evaluated calorimetrically measured
heat capacities,
important families of compounds are still needed,
larly for crystalline solids. There has been an effort to develop
reliable and accurate group contribution schemes to improve
the estimation and compensate for the scarcity of this data. The
simplest schemes are based on first-order additivity and only
enthalpy and entropy of fusion, and heat capacities of several
barbituric acid derivatives measured by differential scanning
calorimetry (DSC). The target compounds (see Figure 1) are
1
6,17
There are several
1,3-dimethylbarbituric acid (1), 5,5-dimethylbarbituric acid (2),
1,3-diethylbarbituric acid (3), 1,3,5-trimethylbarbituric acid (4),
1,5,5-trimethylbarbituric acid (5), and tetramethylbarbituric acid
1
8,19
but new data on the heat capacity of
2
0,21
particu-
(6). The main objective of this work was to expand the database
of available experimental heat capacities of barbituric acid
derivatives and to provide reliable data to adjust and refine group
contribution schemes for the estimation of this property for
compounds that have not yet been investigated.
2
2,23
consider the constituent groups of the molecule.
Other
Experimental Procedures
*
To whom correspondence should be addressed. E-mail (M.V.R.):
Materials. 1,3-Dimethylbarbituric acid (1) [CAS 769-42-6]
and 5,5-dimethylbarbituric acid (2) [CAS 24448-94-0] were
commercially available from Fluka, and no further purification
was necessary as described below.
1,3-Diethylbarbituric acid (3) [CAS 32479-73-5] was obtained
by the condensation of malonic acid with N,N′-diethylurea
victoriaroux@iqfr.csic.es.
†
Institute of Physical Chemistry “Rocasolano”.
Current address: Department of Physical Chemistry, Universidad de Alcal a´ ,
‡
2
8871 Alcal a´ de Henares (Madrid), Spain.
Institute of Medical Chemistry.
PerkinElmer Espa n˜ a S.L.
§
|
⊥
University of Missouri-St. Louis.
1
0.1021/je1008944  2011 American Chemical Society
Published on Web 12/22/2010

2
64 Journal of Chemical & Engineering Data, Vol. 56, No. 2, 2011
concentrated to give crystals of 6, with an mp of 382.3 ( 0.2
3
6
1
K (lit. mp (382 to 383) K); H NMR (300 MHz, CDCl
.54 (s, 6 H), 3.30 (s, 6 H) ppm.
Purity Control. All samples were carefully dried under
3
): δ )
1
vacuum. A determination of purity was assessed by high-
performance liquid chromatography (HPLC) and DSC, using
38
the fractional fusion technique. The mole fraction of impurities
in all compounds studied was less than 0.0001 as assessed by
both techniques.
The standards used for DSC calibration were hexafluoroben-
zene, 0.999 mass fraction, supplied by Aldrich, benzoic acid
National Institute of Standards and Technology (NIST) standard
reference sample 39j, and high-purity indium (w > 0.99999)
and tin supplied by Perkin-Elmer.
Apparatus and Procedure. The behavior of the samples as a
function of temperature was studied by DSC. A Pyris 1
instrument from Perkin-Elmer equipped with an intracooler unit
was used to monitor purity, to study the fusion process and the
possible existence of phase transitions in the solid samples, and
to determine heat capacities as a function of temperature. The
apparatus was previously calibrated in temperature and energy
with reference materials. Temperature and power scales were
Figure 1. Molecular structures of the barbituric acid derivatives studied.
promoted by acetic anhydride according to a literature proce-
33
dure. The oily crude 3 slowly underwent a partial crystalliza-
tion, and the crystals were filtered out with suction and were
washed with a little ethanol. The crystals were recrystallized
3
9
-1
calibrated at heating rates of (0.04 and 0.17) K ·s . The
temperature scales were calibrated by the melting temperature
of the high-purity reference materials, hexafluorobenzene, tin,
3
3
several times to a melting point (mp) of (325 to 326) K (lit.
40
mp 325 K), from mixtures of chloroform and heptane (1.4:1),
in the following manner: the solution was allowed to evaporate
at room temperature until 1,3-diethylbarbituric acid was a liquid
and indium. The power scales were calibrated with high-purity
4
0
indium.
Table 1. Group Values (Γ) Used to Estimate Total Phase Change
Entropies and Heat Capacities
layer on the bottom, and the mass was then cooled to 277 K
1
and seeded. H NMR (300 MHz, CDCl
3
): δ ) 1.21 (t, J ) 7.1
a
a
Γ(∆tpceS(Tfus)) Γ(Cp,m(cr))
Hz, 6 H), 3.65 (s, 2 H), 3.94 (q, J ) 7.1 Hz, 4 H) ppm.
,3,5-Trimethylbarbituric acid (4) [CAS 7358-61-4] was
prepared from diethyl methylmalonate and N,N′-dimethylurea
components
group (Γ)
sR
J· K- · mol-1 J·K-1 ·mol-1
1
1
3
primary sp
carbon
CH
3
17.6
36.6
34
according to a literature procedure and was purified as follows:
The sodium barbiturate salt smoothly precipitated in the reaction
mixture and was filtered out and washed with ethanol. The salt
was dissolved in water, benzene was then added, and the salt
was acidified adding with stirring 1 M hydrochloric acid to a
pH 4. The benzene layer was separated, dried over sodium
sulfate, filtered, and concentrated, giving on cooling, crystals
3
secondary sp carbon sCH
2
s
7.1
26.9
24.6
3
cyclic secondary sp
carbon
cyclic tertiary sp
carbon
aromatic tertiary sp dCHs
carbon
aromatic quaternary dCRs
sp carbon
3
sCH(R)s
-14.7
-34.6
11.7
17.5
8.5
2
2
3
3
4
cyclic quaternary sp sC<(R)
2
s
6.1
of 3, with an mp of 362.7 ( 0.5 K (lit. mp (362.7 to 363.2)
carbon
1
K); H NMR (300 MHz, CDCl
H), 3.31 (s, 6 H), 3.48 (q, J ) 7.5 Hz, 1 H) ppm.
,5,5-Trimethylbarbituric acid (5) [CAS 702-47-6] was
obtained by condensation of diethyl dimethylmalonate with
3
): δ ) 1.61 (d, J ) 7.5 Hz, 3
cyclic sec amide
cyclic tertiary
amide
N-substituted cyclic sC(dO)N(R)C(dO)s
imide
sC(dO)NHs
sC(dO)NRs
2.7
-21.7
46.4
45.3
b
c
1
[-13.6]
[49.4]
cyclic imide
cyclic urea
cyclic ketone
sC(dO)N(H)C(dO)s
sNHC(dO)NHs
[2.8]
[74.1]
[63.6]
34.3
3
5
methylurea, using one equivalent of sodium ethoxide in
ethanol as the condensation agent. In this manner, the sodium
salt of 1,5,5-trimethylbarbiturate smoothly precipitated from the
reaction mixture and was filtered out, washed with ethanol, and
dried in air. The salt was then acidified by quickly adding an
equivalent amount of 6 M hydrochloric acid with vigorous
mixing to prevent the decomposition of the salt in aqueous
solution. Compound 5 was recrystallized from chloroform to
a
b
Values in brackets are considered tentative assignments. This
value, previously assigned tentatively as [52.7], has been modified as a
c
result of additional data. New assignment.
Table 2. Temperatures and Enthalpies and Entropies of Fusion for
the Compounds Studied
a
3
6
T
fus
∆
expt calc
fusH(Tfus) ∆fusS(Tfus) ∆tpceS(Tfus)
the required purity, with an mp of 434.6 ( 0.2 K (lit. mp
kJ· mol- J · K-1 · mol-1 J·K-1 ·mol-1
1
1
K
(
434 to 435) K); H NMR (300 MHz, CDCl
3
): δ ) 1.56 (s, 6
H), 3.28 (s, 3 H), 8.91 (br, 1 H) ppm.
1,3-dimethylbarbituric 396.1 ( 0.3 17.7 ( 0.1 44.6 ( 0.3
44.4
3
7
acid
Tetramethylbarbituric acid (6) [CAS 13566-66-0] was
prepared by methylation of the sodium salt of 1,5,5-trimethyl-
barbituric acid in the following manner. The sodium salt
5
1
,5-dimethylbarbituric 549.3 ( 0.9 37.9 ( 0.3 69.0 ( 0.5
50.6
acid
,3-diethylbarbituric
326.8 ( 0.2 19.6 ( 0.1 60.1 ( 0.3
58.6
acid
(
obtained as described above, 28.3 g, 0.147 mol) was reacted
with methyl iodide (18.5 mL, 0.297 mol) in absolute ethanol
500 mL) at room temperature for 2.5 h. The ethanol was
1,3,5-trimethylbarbituric 362.6 ( 0.5 13.7 ( 0.6 37.7 ( 0.5
47.3
acid
1
,5,5-trimethylbarbituric 434.5 ( 0.2 30.2 ( 0.1 69.6 ( 0.2
51.8, 43.8
45.0
(
acid
removed, and water (75 mL) was added, followed by extraction
with petroleum ether (300 mL) and diethyl ether (300 mL). The
combined extracts were dried over sodium sulfate, filtered, and
tetramethylbarbituric
382.2 ( 0.2 18.5 ( 0.8 48.4 ( 2.1
acid
a
Values calculated according to ref 44.

Journal of Chemical & Engineering Data, Vol. 56, No. 2, 2011 265
Table 3. Mean Experimental Cp,m(cr) Values
p,m(cr)/J·K- ·mol-1
1
C
p,m(cr)/J·K-1 ·mol-1
C
T/K
1
2
3
4
5
6
T/K
2
5
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
68.15
70.15
75.15
80.15
85.15
90.15
95.15
98.15
00.15
05.15
10.15
15.15
20.15
25.15
30.15
35.15
40.15
45.15
50.15
55.15
60.15
65.15
70.15
75.15
80.15
85.15
90.15
175.7
176.7
178.7
180.8
182.6
185.3
187.4
188.5
189.5
191.6
193.9
197.5
199.9
202.7
204.9
206.8
208.9
211.5
214.3
216.9
219.7
223.5
227.2
173.9
175.5
179.2
182.2
184.4
187.0
188.8
190.5
191.4
194.5
196.5
199.1
201.5
203.3
205.3
207.5
208.9
211.2
214.3
217.5
219.2
220.9
222.4
226.2
228.2
228.4
232.0
223.4
225.6
230.7
234.5
238.2
242.1
246.1
248.5
250.3
254.2
259.8
207.8
209.3
213.0
217.0
220.6
224.7
228.5
230.9
232.6
236.6
241.1
244.1
249.4
253.2
258.1
265.1
272.4
199.9
200.9
203.2
205.3
207.5
209.8
212.2
213.6
214.6
216.7
218.9
221.4
223.9
225.6
227.8
230.3
233.0
235.5
237.8
241.0
243.0
246.0
249.2
251.1
253.4
256.3
259.8
217.2
218.1
221.0
223.6
226.4
229.3
232.2
234.2
235.4
238.6
243.0
246.5
249.6
252.3
255.0
258.8
261.8
264.8
268.6
272.1
276.3
280.0
285.1
395.15
400.15
405.15
410.15
415.15
420.15
425.15
430.15
435.15
440.15
445.15
450.15
455.15
460.15
465.15
470.15
475.15
480.15
485.15
490.15
495.15
500.15
505.15
510.15
515.15
520.15
525.15
233.8
236.0
238.4
240.2
242.3
246.2
247.9
250.7
253.7
255.0
258.9
261.5
264.4
266.9
270.0
273.4
275.8
278.7
282.3
285.4
288.2
292.4
296.6
298.4
301.5
304.5
308.0
264.2
267.3
273.2
276.5
279.4
Table 4. Coefficients of the Fitted Curves
2
3
5
a
range
K
A
B·10
C·10
D·10
rmsd
J·K- ·mol-1
1
J·K-1 ·mol-1
J·K-1 ·mol-1
J·K-1 ·mol-1
R2
J·K-1 ·mol-1
1
2
3
4
5
6
268-370
268-525
268-310
268-340
268-415
268-370
189.0 ( 0.1
190.4 ( 0.1
248.4 ( 0.1
230.8 ( 0.1
213.7 ( 0.1
234.7 ( 0.1
45.3 ( 0.3
48.7 ( 0.3
82.8 ( 0.4
75.3 ( 0.7
45.1 ( 0.3
61.5 ( 0.4
0.20 ( 0.17
-0.73 ( 0.04
5.15 ( 0.50
1.31 ( 0.24
-0.40 ( 0.10
0.32 ( 0.19
1.15 ( 0.22
0.39 ( 0.01
12.00 ( 2.4
8.77 ( 0.92
1.17 ( 0.07
1.00 ( 0.26
0.9988
0.9997
0.9997
0.9990
0.9994
0.9991
0.6
0.7
0.1
0.6
0.5
0.6
a
Root-mean-square deviation.
4
2
Thermograms of samples hermetically sealed in aluminum
pans were recorded in a nitrogen atmosphere. All of the pans
with the samples were weighed on a Mettler AT21 microbalance
values. As a check of the experimental method, heat capacity
experiments were performed with benzoic acid in the temper-
3
0
ature interval T ) (268 to 360) K. The relative percentage
error of our measurements in comparison with those reported
in the literature was less than 2 %.
-6
with a detection limit of 1 ·10 g, before and after the
experiments to confirm that no product had volatilized.
After calibration, several runs with high-purity benzoic acid
and indium were performed under the same conditions as the
experimental determinations. The accuracies associated with
measurements of temperature and enthalpy of fusion were
calculated as the percentage deviation of the experimental data
3
0
The mass of sapphire used in each run was 0.030345 g. For
heat capacity determinations, three to six fresh samples weighing
(10 to 25) mg were scanned for each solid compound in the
temperature range from T ) 268 K to its melting temperature
at 0.17 K ·s . The complete temperature range for determination
of heat capacity was divided in intervals of approximately 40
K, overlapping by 5 K from one interval to another.
The molecular weights used to convert the specific heat
capacities measured to their molar values were calculated from
the atomic weights recommended by the International Union
of Pure and Applied Chemistry (IUPAC) in 2005.
Estimations of Total Phase Change Entropies and Heat
Capacity. Total phase change entropies were calculated accord-
ing to the protocol described previously. Table 1 lists group
values used together with the ring equation developed, eq 1, to
estimate ∆tpceS(Tfus
-1
4
0
with respect to the values given in the literature; in all cases
the deviations were less than 1 K and 2.0 % for temperature
3
0
and enthalpy determinations, respectively.
For the determination of purity, temperature, and enthalpy
-1
of fusion, a heating rate of 0.04 K ·s was used, and five to
eight samples weighing (1 to 2) mg were measured. A fresh
sample was used for each run. All compounds showed thermal
stability during the fusion process.
4
3
1
6
-1
Different scans at heating rates of (0.04 and 0.17) K ·s were
performed to determine the possible existence of phase transi-
tions in the samples over the temperature range from T ) 268
K to their melting temperature.
calc
) .
Heat capacities were determined by the “scanning method”
∆tpceS(T ) ) 33.4 + 3.7(N - 3)
(1)
41
fus calc
following the experimental methodology previously described
with synthetic sapphire (R-aluminum oxide) as reference
4
0,41
material.
DSC is a commonly accepted method for the
The estimation of a monocyclic heterocycle begins by first
estimating the parent hydrocarbon of ring size N, obtained by
substituting carbon for all the ring heteroatoms using eq 1.
quantitative determination of heat capacities, and it has been
proven as a suitable technique for obtaining reliable and accurate

2
66 Journal of Chemical & Engineering Data, Vol. 56, No. 2, 2011
Estimations of the heterocyclic ring is then completed by
identifying the appropriate groups that modify the structure and
adding their contributions. The groups are identified in columns
Table 5. Heat Capacity of Compounds Used to Update Group
Values for a Cyclic Tertiary Amide and N-Substituted Urea
C
p,m(cr, 298.15 K)
J·K-1 ·mol-1
a
1
3
and 2 of Table 1, and their contributions are listed in column
of the table. The barbituric acid derivatives of this study were
∆Cp,m
J ·K-1 ·mol-1
compound
imidazolidin-2-one
N,N′-trimethyleneurea
parabanic acid
exp.
calc.
ref
modeled as derivatives of cyclohexane. Modifications to the
cyclohexane structure include the introduction of a cyclic amide
and cyclic imide to the ring. The estimation is then completed
by adding the contributions of any acyclic groups attached to
the ring and modifying any ring carbons atoms that differ from
107.7
129.5
168.9
141.1
188.5
248.5
190.5
228.7
230.9
213.6
234.2
131.8
156.9
157
112.8
137.4
120.5
145.1
192.5
246.3
199.8
253.6
216.2
210.6
247.2
124.6
160.1
160.1
150
-5.1
-7.9
48.4
-4
-4.0
2.2
-9.3
-24.9
14.7
3.0
-13.0
7.2
-3.2
-3.1
13
12.5
-13.1
1.9
45
45
46
14, 15
this work
this work
this work
13
this work
this work
this work
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
47
b
barbituric acid
1
1
,3-dimethylbarbituric acid
,3-diethylbarbituric acid
3
5,5-dimethylbarbituric acid
,5-diethylbarbituric acid
1,3,5-trimethylbarbituric acid
,5,5-trimethylbarbituric acid
the secondary sp hybridized methylene groups found in the
5
parent ring. In some cases, it is possible to model total phase
change entropies in more than one manner. The estimation of
1
tetramethylbarbituric acid
uracil
1,5,5-trimethylbarbituric acid serves as an example. In addition
1
3
5
6
1
3
-methyluracil
-methyluracil
-methyluracil
-methyluracil
,3-dimethyluracil
,6-dimethyluracil
to the ring contribution, the molecule can either be modeled as
a cyclic imide and an N-substituted cyclic tertiary amide or as
an N-substituted cyclic imide and a cyclic secondary amide.
Ideally both values calculated in this manner should be identical.
In this case it is not possible to preferentially assign one value
over the other since both the cyclic imide and the N-substituted
cyclic imide are still tentative values. Both estimated values
are included below in Table 2.
The group values for estimating Cp,m(cr) of the compounds
of this study are listed in column 4 of Table 1. The group value
for a cyclic tertiary amide (old value 52.7), previously assigned
as tentative, has been updated, and a new group value, that for
a N-substituted cyclic imide, has been tentatively assigned due
to the inclusion of new data. The new values were evaluated by
163
162.5
182.5
187.4
188.1
187.6
191.1
212.6
244.5
241.1
302.7
358.1
241.8
287.2
296.4
252.9
150
195.6
185.5
185.5
185.5
175.4
221.0
246.4
247.9
274.8
301.7
247.9
274.8
301.7
247.0
271.6
296.2
142.1
138.2
142.1
145.8
141.3
182.8
169.5
135
1,6-dimethyluracil
2.6
2.1
1
5
,5-dimethyluracil
,6-dimethyluracil
15.7
-8.4
-1.9
-6.8
27.9
56.4
-6.1
12.4
-5.3
5.9
11.3
18.3
-2.7
0.1
-5.4
-1.1
9.6
1,3,6-trimethyluracil
1
1
,3,5,6-tetramethyluracil
,3-dimethyl-5-ethyluracil
1,3-dimethyl-5-propyluracil
b
1
1
1
,3-dimethyl-5-butyluracil
,3-dimethyl-6-ethyluracil
,3-dimethyl-6-propyluracil
1,3-dimethyl-6-butyluracil
1
1
,3-dimethyl-5,6-trimethyleneuracil
,3-dimethyl-5,6-tetrarmethyleneuracil 282.9
1,3-dimethyl-5,6-pentamethyleneuracil 314.5
6
5
-chlorouracil
-fluorouracil
139.4
138.3
136.7
144.7
150.9
182.2
167.2
145
147
166.2
189
231.8
131.4
268.2
294.6
minimizing the following function: ∑[[Cp,m(cr)exp - Cp,m(cr)calc]/
2
C
p,m(cr)exp] , using the data in Table 5.
5-chlorouracil
5
5
5
5
5
6
6
6
-bromouracil
-iodoracil
-trifluoromethyuracil
-nitrouracil
-aminouracil
-aminouracil
-amino-1-methyluracil
-amino-1,3-dimethyluracil
47
47
47
48
48
48
48
49
-0.6
-2.3
10
Results and Discussion
Fusion temperatures and enthalpies and experimental entropies
of fusion of the compounds measured are given in Table 2. The
uncertainties were taken as the standard deviation of the mean.
135
12
170.5
206.0
204.2
123.3
266.6
277.0
-4.3
-17.0
27.6
8.1
1.7
17.6
caffeine
succinamide
antipyrine
Tfus values are reported as DSC onset temperatures. Also
49
49
49
included in the last column of the table is the estimated total
44
4-aminoantipyrene
phase change entropy, ∆tpceS(Tfus). This term includes the total
phase change entropy associated in going from T ) 0 K to the
liquid at T ) Tfus. For compounds without any other phase
transitions, this entropy change is identical to the fusion entropy.
The uncertainty associated with predicting total phase change
entropies by this method based on approximately 1000 estima-
a
b
Cp,m(cr, 298.15 K, expt.) - Cp,m(cr, 298.15 K). Not used in
generating the group value for a cyclic tertiary amide.
The range studied for each compound, the coefficients of the
fitted third-order equation in temperature, and the root-mean-
square deviation (rmsd) for all the compounds are collected in
Table 4. To our knowledge, there are no Cp,m data in the
literature for comparison with our results.
tions is ( 18.5 J ·K- ·mol . For the most part, the estimations
reported in Table 2 fall well within this uncertainty, suggesting
the absence of any substantial low temperature solid-solid phase
transitions. To the authors’ knowledge, there is no other
calorimetric data in the literature for comparison with the results
obtained in this study.
1
-1 25
Estimations of heat capacities at T ) 298.15 K are relatively
straightforward. The estimation requires an identification of the
correct groups and evaluating their sum. As noted in the
Experimental Section, one group value previously assigned as
tentative has been updated, and one additional value, an
N-substituted cyclic imide, has been added. The compounds and
data used for this purpose are included in Table 5, which
includes experimental values from this work as well as from
the recent literature. All of the compounds in Table 5, except
for parabanic acid and 1,3-dimethyl-5-butyluracil, were used
in generating the new group values. These two compounds
resulted in errors greater than three standard deviations when
included in the correlations and were therefore excluded. The
No solid-solid phase transitions were observed over the
temperature interval from T ) 268 K to the corresponding
melting points for any of the compounds.
The measured molar heat capacities as a function of temper-
ature for all compounds are collected in Table 3. The values
given in Table 3 are averages of three to six independent runs.
The standard deviation of all of the data associated with multiple
measurements is less than 2 J ·K- ·mol .
1
-1
The experimental results for the compounds were fit to a third-
order polynomial in temperature of the type:
-1
-1
heat capacity of 1,3-dimethyl-5-butyluracil (351.8 J ·K ·mol )
is particularly surprising since the value for the isomer, 1,3-
-
1
-1
Cp,m(cr) ) A + B(T/K - 298.15) +
dimethyl-6-butyluracil (296.4 J ·K ·mol ), is considerably
lower. The two isomers differ only in the location of the butyl
group on the heterocyclic ring. The standard deviation associated
2
3
C(T/K - 298.15) + D(T/K - 298.15) (2)

Journal of Chemical & Engineering Data, Vol. 56, No. 2, 2011 267
-
1
-1
with the estimations listed in Table 5 was ( 11.0 J·K ·mol .
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This increases to ( 14.9 J·K- ·mol if the uncertainties
1
-1
associated with the two outliers are included.
(
(
Some flexibility also exists in the estimation of Cp,m(cr). As
described above, 1,5,5-trimethylbarbituric acid (5) can be
estimated as either a cyclic imide attached to a cyclic tertiary
amide, 235.3 J ·K- ·mol , or as an N-substituted cyclic imide
1
-1
-1
-1
attached to a cyclic secondary amide, 210.6 J ·K ·mol . In
principle, both estimations should produce identical results. In
general, the use of different groups in an appropriate manner
usually results in Cp,m(cr) values that do not vary a great deal
from each other. In this case the later value is preferred because
the former calculation uses a value that is still tentatively
(
(
assigned, [74.1] J ·K- ·mol . 5,5-Dimethylbarbituric acid (2)
1
-1
has been estimated as the sum of a cyclic urea and cyclic
secondary amide in Table 5, 199.8 J ·K- ·mol . An alternative
1
-1
method, perhaps less indicative of the properties of the molecule,
is to estimate Cp,m(cr, 298.15 K) as the sum of a cyclic urea
and two cyclic ketones. This results in the value 211.5
-1
-1
J·K ·mol , not terribly different from the experimental value
(
-1
-1
of 190.5 J ·K ·mol .
The uracils in Table 5 were previously estimated by Zielen-
using this group method. Uracil was estimated
as the sum of two cyclic secondary amides and two tertiary
aromatic sp C, 127.8 J ·K ·mol . If this protocol is applied
using the older group value previously available for a cyclic
47,48
kiewicz et al.
2
-1
-1
(
17) Chickos, J. S.; Hosseini, S.; Hesse, D. G.; Liebman, J. F. Heat Capacity
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-1
-1 22
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-1
-1
of 170.7 J ·K ·mol is calculated, which differs from the value
4
, 271–278.
of 153.5 J ·K- ·mol reported in Table 2 of ref 47. It is not
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1
-1
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aromatic sp C was intended for aromatic compounds and would
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2
group value for a cyclic tertiary sp carbon is recommended
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JE1008944