Solvents, acceptor properties hydrogen bonded

Methoxypurine was found to crystallize as a hemihydrate from /V,/V -dimethyl formamide, and as a trihydrate from water [63]. Thermal treatment of the trihydrate could be used to obtain the hemihydrate. Zafirlukast was obtained in the form of monohydrate, methanol, and ethanol solvatomorphs, with the drug substance adopting a similar conformation in all three structures [64], In the isostructural methanol and ethanol solvates, the solvent molecules are hydrogen-bonded to two zafirlukast molecules, while in the monohydrate, the water molecules are hydrogen-bonded to three zafirlukast molecules. The structures of the acetone and isopropanol solvatomorphs of brucine have been reported, where the solvent controlled the self-assembly of brucine on the basis of common donor-acceptor properties [65],... 

Water is both a donor and acceptor of hydrogen bonds. Consequently, in bulk solvent, water molecules are extensively hydrogen bonded to each other. These are relatively weak bonds ( 5 kcal/mol) and, at physiological temperature, are rapidly broken and reformed. However, the hydrogen-bonding network affects many of the properties of water. 

The efficiency of postsynthetic acetylation of the Hmb groups is well demonstrated by the successful synthesis of the extremely insoluble P-amyloid-(1 3) peptide.P Additional examples of the advantageous use of this backbone protection are the recent syntheses of N-glycopeptidesf and phosphopeptides.t There are, however, also cases where even with multiple backbone protection only noinor improvements in solubility were obtained,and polar aprotic solvents with strong hydrogen-bond acceptor properties, such as DMSO, proved to be more efficient. ... 

Various attempts have been made to classify solvents, e.g. according to bulk and molecular properties empirical solvent parameter scales hydrogen-bonding ability and miscibility >. In table I solvents are divided into classes on the basis of their acid-base properties which can be used as a general chemical measure of their ability to interact with other species. Detailed information on these and other solvents, their symbols, fusion and boiling pointe and Gg), bulk properties (6,Ti, q), and currently-used correlation parameters DN (donor number), Ej-value, and AN (acceptor number) is given in Appendix A-1. 

The term aprotic is often used in a more restricted sense to denote solvents such as the hydrocarbons which are essentially devoid of any acid-base properties, and which act neither as donors nor as acceptors in hydrogen bond formation. 

The choice of solvent is of particular importance. First, it has to be chosen such that the solubility is in a suitable range for the selected type of crystallization experiment (reasonably high solubility for cooling experiments, very low solubility in solvents used for precipitation, etc.). Second, it is important to use solvents with diverse physical properties in order to explore the whole parameter space of possible environments. In addition to molecular solvent-solute interactions, bulk properties of solvents such as viscosity may play a role. Gu et al. [19] examined 96 solvents in terms of 8 relevant solvent properties hydrogen bond acceptor propensity, hydrogen bond donor propensity, polarity/dipolarity, dipole moment, dielectric constant, viscosity, surface tension, and cohesive energy density (calculated from the heat of vaporization). Based on all 8 properties, the 96 solvents were sorted into 15 groups... 

Basicity, the property to act as a proton acceptor in hydrogen bonds. This parameter is irrelevant for non-localizing solvents, and alcohols have different selectivity properties. 

Hydrogen bond donor solvents are simply those containing a hydrogen atom bound to an electronegative atom. These are often referred to as protic solvents, and the class includes water, carboxylic acids, alcohols and amines. For chemical reactions that involve the use of easily hydrolysed or solvolysed compounds, such as AICI3, it is important to avoid protic solvents. Hydrogen bond acceptors are solvents that have a lone pair available for donation, and include acetonitrile, pyridine and acetone. Kamlet-Taft a and ft parameters are solvatochromic measurements of the HBD and HBA properties of solvents, i.e. acidity and basicity, respectively [24], These measurements use the solvatochromic probe molecules V, V-die lliy I -4-n i in tan iline, which acts as a HBA, and 4-nitroaniline, which is a HBA and a HBD (Figure 1.17). 

It should be kept in mind that the terms acidity and basicity of the solvent have to be intended not only according to the Lewis concept (electrophilic vs. nucleophilic properties), but also according to the Bronsted concept (proton donor vs. proton acceptors), or to the hydrogen bonding capacity (hydrogen bond donor vs. hydrogen bond acceptor). 

Investigation of stable simple enols has recently been undertaken with a series of p,P-dimesityl-a-ethenols [29] and [30] in which Mes = 2,4,6-tri-methylphenyl. In this work, 5(OH) and /hcoh were measured for a series of compounds with various a-substituents and in a range of solvents (Biali and Rappoport, 1984 Rappoport et al., 1988). The nmr parameters were shown to be linearly related to the Kamlet and Taft P-variable, a solvent property that is related to its ability to act as a hydrogen-bond acceptor (Kamlet and Taft, 1976 Taft et al., 1985). 

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