Oxidative addition of N-aminophthalimide to styryl-1,2,4-oxadiazoles

Abstract

The oxidation of N-aminophthalimide with lead tetraacetate in the presence of 5-[(Ε)-2-arylethenyl]-3-(4-methylphenyl)-1,2,4-oxadiazoles and 5-(4-methylphenyl)-3-[(Ε)-2-phenyl-ethenyl]-1,2,4-oxadiazole led to the formation of the corresponding (3-aryl-1-phthalimidoaziridin-2-yl)-(4-methylphenyl)-1,2,4-oxadiazoles. In the reaction with 3,5-distyryl-1,2,4-oxadiazole a mixture was obtained of two regioisomeric monoadducts and a diadduct in the ratio 80 : 15 : 5; at the use of 3 equiv of the aziridinating reagents only diadduct was isolated as a mixture of two diastereoisomers in the ~3 : 2 ratio that were separated by recrystallization.The oxidative phthalimido-aziridination of alkenylsubstituted pyrazoles and 1,3,4-oxadiazoles proceeds at the exocyclic C=C bond and affords cleanly the corresponding aziridinylazoles [1,2]. In this connection the evaluation of the applicability range and revealing the regular trends of this reaction as a general method for designing linearly connected polyheterocyclic systems containing aziridine fragment is an urgent task. To this end we selected styryl-substituted 1,2,4-oxadiazoles fairly different from its isomers, symmetric 1,3,4-oxadiazoles.Initial unsaturated 1,2,4-oxadiazoles IIa-IIe were obtained by procedure [3] through the thermal cyclization of acylation products of amidoximes Ia, Id prepared from p-tolunitrile or cinnamonitrile and hydroxylamine (Scheme 1) [3].The 1 H NMR spectra of styryl-1,2,4-oxadiazoles IIaIIe in the region δ 7.0-8.0 ppm contain doublets of the olefin protons with 3 J 15-17 Hz indicating the retention of the trans-location of these protons in the course of the cyclization. In their 13 C NMR spectra the carbon atoms of the heterocycle at δ 168-169 (C 3 ) and ~175 ppm (C 5 ) are characteristic; they are shifted downfield by 5-10 ppm compared with the carbon atoms of the isomeric 1,3,4-oxadiasoles (cf.[2]).The oxidative addition of the N-aminophthalimide to styryloxadiazoles IIa-IIe was carried out by the standard procedure adding in turns by small portions N-aminophthalimide and lead tetraacetate to the solution of the unsaturated compound in dichloromethane [2]. We established in the preliminary runs with IIa substrate (from the 1 H NMR spectra of the reaction mixtures) that at cooling the solution from the room temperature to -10°C the conversion of the initial compound considerably grew, but further cooling practically did not affect the rate of the process, therefore all subsequent reactions were performed at-10°C. The composition of separated R 1 = C 6 H 4 Me-p, R 2 = CH=CH-Ph (a), CH=CH-C 6 H 4 OMe-p (b), CH=CH-C 6 H 4 NO 2 -p (c); R 1 = CH=CH-Ph, R 2 = C 6 H 4 Me-p (d), CH=CH-Ph (e). Scheme 1.

Oxidative Aminoaziridination of 2‐Vinylfuran Derivatives as an Approach to Hexa‐2,5‐diene‐1,4‐dione Monohydrazones

“…Hydrazone 3a was obtained as as ingle product, and between the two standard oxidants (Pb(OAc) 4 vs. PhI(OAc) 2 ), we found Pb(OAc) 4 to be more effective at À20 8Ca nd provide compound 3a in 55 %yield.…”

“…Previously,w es ynthesized as et of heterocyclic-substituted aziridines througha no xidative addition of N-aminophthalimidet ot he exocyclic C=Cb ond of alkenylsubstituted pyrazoles, [3] 1,2,4-oxadiazoles, [4] and 1,3,4-oxadiazoles. [5] However,thiophene, selenophene, [6] indoles, [7] and benzo [b]furans [8] have afforded stable fused aziridines under the same conditions.…”

“…[21] Finally,t og ain insighti nto the mechanism of the described transformation,w ee valuated two possible pathways to the phthaloylhydrazones( Scheme 9). The proposed mechanism includes aziridination of the heterocycle followed by the rearrangemento fu nstable fused aziridine of type A.A tt he same time, an easy oxidation of furan by treatment with meta-chloroperoxybenzoic acid (m-CPBA), [23] Pb(OAc) 4 , [24] dimethyldioxirane, [25] or titaniums ilicalite 1/H 2 O 2 [26] is known to lead to a1 ,4-dicarbonyl species. For example, (Z)-1,2-diaroylethenes were obtained from 2,5-diarylfurans by using the same oxidant (Pb(OAc) 4 )a si no ur work.…”

“…The successive addition of N-aminophthalimide (1.2 equiv)a nd Pb(OAc) 4 (1.2 equiv) at À20 8Ct os olutionso f2k and 2l,r espectively,was carriedo ut and then repeated at À10 8Ct ogive aziridines 5k and 5l as single products (Scheme 6). These aziridines were obtained as mixtures of two isomers with regardt o the C=Nbond, and each isomer existed as two invertomers because of the slow inversion of aziridine nitrogen atom.…”

“…[24] Therefore, in principle, the key step could be ar eaction of ad icarbonyl compound of type B with N-aminophthalimide. To examine this second hypothesis, Pb(OAc) 4 was added to the model substrate 2a in the absence of N-aminophthalimide. According to TLC and NMR analysis, only the startingm aterialw as present in the reaction mixture after 3hat À20, 0, and 20 8Ci neither the presenceo ra bsence of K 2 CO 3 .H owever,t he formation of the phthaloylhydrazones usually occurred within 1h at À20 8C.…”