Tautomerism, Regioisomerism, and Cyclization Reactions of Acridinyl Thiosemicarbazides.

Abstract

Acridine derivatives R 0430Tautomerism, Regioisomerism, and Cyclization Reactions of Acridinyl Thiosemicarbazides. -The behavior of methyl-and phenylhydrazine (II) and (V) in the reaction with isothiocyanate (I) is different, while the reaction of (II) with (I) proceeds regioselectively with the α-nitrogen more nucleophilic than the β-nitrogen, the regioselectivity in the reaction of (V) with (I) is poor but varies with the solvent. Only in the case of ethanol as solvent, the nucleophilic predominance of the α-nitrogen is pronounced. Interestingly, whereas the methyl product exists as an equilibrium mixture of open-chain (III) and spiro thiosemicarbazide (IV), the phenyl thiosemicarbazides (VI) and (VII) exist only as spiro forms. Reaction of (I) with acetone methyl hydrazone (VIII) yields the expected thiosemicarbazide (IX) accompanied by the new ring system (X). Cyclization reaction of (IX) and (X) with the bifunctional electrophiles (XI) afford the spirocycles (XII). -(KLIKA*, K. D.; BALENTOVA, E.; BERNAT, J.; IMRICH, J.; VAVRUSOVA, M.; KLEINPETER, E.; PIHLAJA, K.; KOCH, A.; J. Heterocycl.

Structural revision of products resulting from the reaction of methylhydrazine with acridin-9-yl isothiocyanate due to unexpected acridinyl migration and further reactions

“…The reaction of the material−present as a mixture of open-chain and spiro forms 6 −resulting from the addition of methylhydrazine to acridin-9-yl isothiocyanate (4) with methyl bromoacetate yielded the product 2-[2-(9,10-dihydroacridin-9-yliden)-1-methylhydrazino]-4,5-dihydro-1,3-thiazol-4-one (6) whose structure depicted in Figure 1 was determined by X-ray crystallographic analysis. The 1 H, 13 C, and 15 N chemical shifts of 6 together with all other compounds discussed in this work are compiled in Tables 1 and 2.…”

“…The course of the reaction (see Scheme 2) to provide this structure is easily anticipated from either 2 or 3, the sulfur (as thiol) can displace bromide from methyl bromoacetate followed by spiro ring opening in the case of 2 and then attack of the nitrogen in the urea-type position (imine in both cases) to displace methoxide to form the thiazolinone ring. The quintessential question is then whether it is the spiro form 2 (present 6 in DMSO solution as a minor interconverting species…”

“…Compound 4-(9,10-dihydroacridin-9-yliden)thiosemicarbazide (5), 6 which does not bear a methyl substituent, presumably undergoes the same migration reaction based on the chemical shifts after due allowance for the methyl group lacking. Regarding the 1 H NMR spectra of both 3 and 5, it is, quite naturally, the restricted rotation about the thioamide-type bond that is responsible for the distinctiveness of the NH 2 protons, formerly attributed to internal hydrogen bonding.…”

“…It is through the former structure that isomerization can occur thus resulting in migration of the acridinyl unit from one end to the other of the thiosemicarbazide moiety. As a result, whereas previously 6 we considered the solution equilibrium to be between 4-(9,10-dihydroacridin-9-yliden)-2-methylthiosemicarbazide (1) and 2´-methyl spiro[dihydroacridinyl-9(10H),5´-1´,2´,4´-triazolidine]-3´-thione (2), we are now compelled to modify this to the following system outlined in Scheme 1. Reviews of this type of ring−open-chain tautomerism are present in the literature.…”

“…The solution equilibrium was formerly thought 6 to be between the open-chain form 1 and the spiro form 2 but it has now been determined that the spiro form 2 is in equilibrium with the…”