superior to previously known syntheses of such com-pounds1'h.21.If during the chlorination of (1) in aqueous solution the pH is kept between 3 and 7 (see Experimental) then a maximum yield of the chlorohydrins (2) is obtained without formation of (4) being observed.The arrangement of the substituents on C-3 and C-4 relative to the P--0 group in the chlorohydrins (2) is decisive for the position of the epoxide ring in the epoxides (3). Hence, an X-ray structure analysis was carried out on (2f1) [']. As shown in Figure 1 the hydroxy-and 0x0 groups are situated on the same side of the ring plane.Diastereomeric mixtures of (2) lead also to diastereomeric mixtures of (3), whereas use of the individual diastereomers [(2d,), (2d3, (2f1), (2f2)] affords in each case only one isomer of (3)I"l. In the case of (3a) the isomers could be separated by preparative layer chr~matography[~l. Basically, two configurational isomers (A and B) are conceivable161. R2The structural assignment of the two pairs of isomers (3al)/(3az) and (3d1)/(3d2) must however still remain open[71, whereas in the case of the epoxides (3f1)/(3f2) an assignment of conformation is possible by X-ray structure analysis of (2f1); (Zf,) ought to afford (3fJ as isomer A, while (2f2) ought to give (3f2) as isomer Bi6J. Experimental(2): Chlorine (0.5 mol) is passed into a stirred solution of (1) (0.5 mol) in water (180 ml) at 20-25°C with external cooling and with simultaneous dropwise addition of a solution of sodium carbonate (0.25 mol) in water (100 ml) such that the pH of the mixture is kept between 3 and 7. The mixture is then neutralized, water removed at 40 "C/1.6 x lo-' bar, and the residue stirred with 100 ml CH2C12. Filtration followed by removal of solvent at 3O0C/1.O x lo-' bar affords (2) as colorless crystals.( 3)[']:A solution of sodium hydroxide (0.5 mol) in water (50 ml) is added dropwise to a stirred and externally cooled solution of (2) (0.5 mol) in water 150 ml. After 15 min the mixture is neutralized and worked-up as in the case of (2). Thin-layer chromatographically homogeneous (3) is obtained as a colorless oil or crystals.

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Reaktion die bisher unbekannten, stabilen P-Azolyl-a,a-dicarbonylverbindungen (3) bzw.

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1. A radioimmunoassay (RIA) has been developed for determination of both nomifensine and total nomifensine (nomifensine + conjugated nomifensine) in serum, plasma, and urine. 2. Antibodies were prepared in rabbits by immunization with N‐(8‐Nomifensine) succinamic acid‐ bovine serum albumin. 3H‐labelled drug was used as tracer. Separation of free from antibody‐bound nomifensine was carried out using dextran‐ coated charcoal. For determination of total nomifensine, the acid‐ labile conjugate was split by acidification. 3. The limit of detection for nomifensine is 300 pg/ml plasma and the cross‐reactivity of the metabolites is less that 1%. The influence of conjugated nomifensine on the results of nomifensine can be corrected. 4. Pharmacokinetics of nomifensine were determined in healthy volunteers after oral administration of 100 mg 14C‐labelled drug. Peak levels of 14C radioactivity (2,150 ng/ml), total nomifensine (1,252 ng/ml) and nomifensine (53 ng/ml) appeared within 1.5‐2 h; the half‐life of elimination from plasma was 1.5‐2 hours. The advantages of this routine method are high sensitivity, the requirement of small amounts of plasma, and simple handling.