Electronic Aspects of Chlorpromazine

Association is a feature of chlorpromazine base and related derivatives in the supercooled state. Such associations may be preceded by the formation of intramolecular complexation, i.e., different regions of the same molecular species acting as donor and acceptor. It is interesting to note that in this context the solid state structure of chlorpromazine base is not symmetrical, presumably due to van der Waals or perhaps weak charge transfer interaction between the chlorine ring substituent and the side-chain amine group. Donor and acceptor properties can be modified by chemical substitution, and are sensitive to steric hindrance. In a way, intramolecular charge transfer reproduces the effect of delocalized electrons.  

In this study we have determined by means of H and C NMR spectroscopy the conformation and some electronic aspects of CPZ HCl and CPZ base in a variety of solvents and in the presence of electron acceptors. The NMR experiments were complemented by negative stain electron microscopy. 

Chlorpromazine hydrochloride was a gift from Smith, Kline, and French Co. 10-Methyl phenothiazine was obtained from Eastman Organic, and 2-chlorophenothiazine from Aldrich Co. These compounds were used without further purification. Phenothiazine obtained from Matheson, Coleman, and Bell was vacuum sublimed twice immediately prior to use. CPZ base was prepared by titrating the hydrochloride with 1 N NaOH solution. An ether solution of the base was washed repeatedly with water, and then dried with anhydrous Na2S04. The ether was evaporated, and 

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