Treatment of N,N'-dibenzyl-1,2-diaminobenzene (2) successively with thionyl chloride and then m-chloroperbenzoic acid gave N,N'-dibenzyl-1H,3H-2,1,3-benzothiadiazole 2,2-dioxide (4), which gave (via routes analogous to standard epinephrine syntheses) four bicyclic catecholamine analogues 7a-d. Hydrogenolysis of 4 yielded the parent heterocycle 5 in the first practicable synthesis avoiding expensive sulfamide (Scheme I). The trifluoromethanesulfonamidoacetophenones 8m and 8p on similar elaboration gave triflanilide catecholamine analogues 14m, 14p,17m, and 17p (Scheme II). 4,4'Dimethoxybenzhydrylamine (15) is recommended for the regiospecific synthesis of primary amines from epoxides (Scheme II). Series 7,14, and 17 were inactive in animal cardiovascular screens. Selected compounds were also screened in bronchodilator and in in vitro dopamine-, clonidine-, and prazosin-receptor binding assays as appropriate; again no activity was observed. Steric lipophilicity, and acidity factors are discussed, and the inactivity is ascribed to the high acidity of both systems (pKa approximately equal to 4).
Pyridinium methylides combine with hex-3-yne-2.5-dione. but-3-yn-2-one. methyl but-2-ynoate. methyl phenylacetylenecarboxylate, dimethyl penta-2.3-dienedioate, and ethyl 2-methylbuta-2.3-dienoate and 2-methylpenta-2.3-dienoate to give indolizines, identified from spectra.Road, Oxford OX1 3QU DIETHYL and dimethyl acetylenedicarboxylate 2 and the much less investigated propiolic esters3 give a wide variety of products with nitrogen-cont aining he t erocycles and y l i d e ~, ~ and the reactions of but-3-yn-2-one with some pyridine derivatives have been reportedS6 Few other activated acetylenes and allenes have been examined in this connection and the present paper described some initial investigations.Goldschmidt and Zoebelein have reported the oxidation of hex-3-yne-2,5-diol to the 5-hydroxy-2-one (45%) and the 2,5-dione (1) (10%) by chromium trioxide MeCO-C C-COMe 9 MeCO(ArNH1C =CH.COMe ArNHZ (1) (2) Ar =Ph (3) Ar = 4 -N 0 2 C 6 H ~in aqueous sulphuric acid,? but we found their procedure satisfactory only for preparing a mixture (n.m.r. analysis) of the hydroxy-ketone (65%) and the diketone ( l O ~o ) . The hydroxy-ketone was obtained pure (n.m.r.) by distillation in vacuo from sufficient 4-nitroaniline to convert the diketone into the nitroanilino-derivative (3). None of the diketone was obtained from further oxidation of the hydroxy-ketone under the conditions recommended.6 Only about half the oxidant had been consumed 4 h after its addition, but the amount of diketone isolable at this point or 20 h later was the same. The diketone was apparently oxidized to acetic acid at a rate comparable to that for its formation, and proved difficult to separate from unchanged hydroxy-ketone. Use of manganese dioxide as oxidant in an inert solvent 8 gave a maximum diketone : hydroxy-ketone ratio of 1 : 9 (n.m.r.), the diketone again being further oxidized. The least unsatisfactory but reproducible preparation of hex-3-yne-2,5-dione ( 10-18~o) was the oxidation with chromic acid of a mixture of the diol and the hydroxyketone.Hex-3-yne-2,5-dione is much more reactive than dimethyl acetylenedicarboxylate g towards aniline and 4-nitroaniline, for in methanol, which usually gives the
Durch Quaternisierung von Benzimidazol (I) und anschließende Hydrolyse erhält man das Dibenzyl‐l ,2‐diaminobenzol (II), das nach Cyclisierung zum Monoxid (III) mit Persäure zum Dioxid (IV) oxidiert wird.
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