In
this work, the phase equilibrium solubility of 5-fluorocytosine
(5-FC) in dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), 1-butanol, acetonitrile, 1-propanol, 1,4-dioxane,
acetone, ethyl acetate, 2-propanol, 2-butanone, and mixture systems
(DMSO + 2-propanol and DMF + 2-propanol) at a series of temperatures
(283.15–323.15 K) is determined, and model correlation, solvent
effect, and preferential solvation analysis are researched. The solubility
of 5-FC is related to temperature, which decreases with decreasing
temperature. For monosolvent systems, the mole solubility order is
DMSO > DMF > 1-butanol > 1-propanol > 2-propanol >
acetone > 2-butanone
> 1,4-dioxane > acetonitrile > ethyl acetate. The solvent
effect has
been studied in monosolvents, hydrogen-bonding acceptor (HBA) interactions
and nonspecific dipolarity/polarizability interactions favor dissolution,
and solvent self-cohesiveness is not beneficial to dissolution. For
two mixture systems, the mole solubility of 5-FC in DMSO + 2-propanol
solvent systems is higher than that in DMF + 2-propanol solvent systems.
A dimensionless parameter (δ) is defined to observe the deviation
from ideality of mixed solvents whose values are all greater than
zero. The equilibrium constant of the solvent exchange process (K
ps) can be used to evaluate the preferential
solvation of 5-FC. DMSO or DMF dissolves 5-FC in the local region
around 5-FC preferentially. The equilibrium solubility data is correlated
by four correlation models (modified Apelblat, λh, CNIBS/R-K, and Jouyban–Acree models). The greatest relative
average deviation (RAD) and root-mean-square deviation (RMSD) values
are 2.01% and 11.87 × 10–5 in pure solvent
systems and 2.20% and 5.99 × 10–5 in mixture
systems, respectively. These four models show excellent correlation
with the experimental solubility data.