Cinzia Tavani

Ring opening of 2-substituted 4-nitrothiophenes with pyrrolidine. Access to new functionalized nitro-unsaturated building blocks

Abstract The reaction conditions of the ring-opening processes of 3-nitrothiophene 7a and of 3-nitrobenzo[b]thiophene 7b with pyrrolidine and silver nitrate were optimized as well as those of the subsequent S-methylation of the ensuing silver enethiolates 8a and 8b to 4-methylthio-2-nitro-1-pyrrolidino-1,3-butadiene 9a and 1-(2-methylthiophenyl)-1-nitro-2-pyrrolidinoethylene 9b. Under such conditions 2-X-substituted 4-nitrothiophenes 7c–i consistently gave good yields of the corresponding 4-methylthio-2-nitro-1-pyrrolidino-4-X-1,3-butadienes 9c–i. The nitroenamine derivatives 9a–i were then reacted with p-tolylmagnesium bromide to furnish moderate to good yields of 4-methylthio-2-nitro-1-(p-tolyl)-4-X-1,3-butadienes 10a,c–i and 1-(2-methylthiophenyl)-1-nitro-2-(p-tolyl)ethylene 10b. Stereochemistry of the interesting building blocks 9a–i and 10a–i was assigned on the grounds of 1H NMR data and NOE experiments.

A novel approach to 1H-indazoles via arylazosulfides

Abstract Treatment of variously substituted ( o -alkylaryl)azosulfides 1a-n with potassium tert -butoxide in DMSO at room temperature smoothly furnishes 1 H -indazoles 2a-n .

α-arylation vs. α-arylhydrazonylation of alkyl aryl ketones with arylazo tert-butyl sulfides

Abstract Potassium enolates of alkyl aryl ketones react selectively in DMSO with phenylazo 1a and 4 -methylphenylazo tert-butyl sulfide 1b undergoing respectively effective α-phenylation via S RN 1 and α-(4-methylphenyl)hydrazonylation via elimination-addition.

Arylation of potassium 2,4-pentanedionate via SRN1 on diazosulfides.

Abstract Potassium 2,4-pentanedionate reacts with diazosulfides (E)-1 and (Z)-2 in DMSO to give 3-aryl-2,4-pentanediones 3 via an S RN 1 process. Advantages and drawbacks of such new access to 3 are reported together with relevant mechanistic implications.

SRN1 C-arylation of phenols by azosulfides; A novel synthesis of dibenzo[b,d]pyran-6-ones

Abstract The ortho-arylation of phenols by (2-cyanoaryl)azo t-butyl (or phenyl) sulfides in SRN1 conditions, followed by a silica-gel-catalysed lactonisation of the resulting 2-cyano-2′-hydroxybiphenyls, leads to dibenzo[b,d]pyran-6-ones.

Behaviour of Arylazo tert-Butyl Sulfides with Ketone Enolates. Competition between SRN1 α-arylation and Azocoupling Reactions.

Abstract (Z)-Arylazo tert-butyl sulfides 1a-i react, in DMSO and at room temperature, with potassium acetone enolate to give good yields of 1-aryl-2-propanones via spontaneous SRN1 dark reactions, α-Phenylation of pinacolone and acetophenone enolates by 1a likewise occurs in excellent yields. In agreement with the involvement of an electron-transfer catalyzed chain process, the reaction of the 4-bromo derivative 1n with pinacolone enolate gives mainly the bis-substitution product 13. With azosulfides 1j–m the arylation pathway competes with a base-induced thiol elimination eventually leading, depending on the structure of the azosulfide, to indazoles 8 or 11 and/or to 2-oxopropanal arylhydrazones 9, 10 or 12.

Pyrrolidines, Pyrrolines and Pyrroles from 1,4-Diaryl-2,3-dinitro-1,3-butadienes via a 5-endo-trig Cyclization

The reactions between 1,4-diaryl-2,3-dinitro-1,3-butadienes 1a-d and primary alkylamines gave high yields of N-alkyl-2,5-diaryl-3-alkylamino-4-nitropyrrolidines 2 as pure all-trans diastereomers via an unusually favoured 5-endo-trig ring closure. The stereochemistry of compounds 2 has been attributed through an X-ray crystal structure analysis of the acetyl derivative 5 of 2ai. Amine elimination from 2 gave the N-alkyl-2,5-diaryl-3-nitro-3-pyrrolines 3 which could be easily aromatized to the corresponding pyrroles 4.

Access to 3-arylmethyl-5-(methylthio))isoxazoles via an initial ring-opening of 2-methylthio-4-nitrothiophene

Abstract The reactions of 1,1-bis(methylthio)-3-nitro-4-pyrrolidino-1,3-butadiene (deriving from the initial ring-opening of 2-methylthio-4-nitrothiophene with pyrrolidine and silver nitrate in EtOH) with arylmagnesium bromides result in the chemoselective replacement of the pyrrolidino group with the aryl moiety of the Grignards. The 4-aryl-1,1-bis(methylthio)-3-nitro-1,3-butadienes thus obtained are the key intermediates for the effective synthesis, through the corresponding reduction products 4-aryl-3-hydroximino-1,1-bis(methylthio)-1-butenes, of the previously unknown 3-arylmethyl-5-(methylthio)isoxazoles.

From 3,4-dinitrothiophene to 1,2-diaryl-4-nitrobenzenes through (E,E,E)-1,6-diaryl-3-nitro-1,3,5-hexatrienes

Abstract The reactions between 1,2-bis(diethylamino)-2,3-dinitro-1,3-butadiene, easily obtainable by ring-opening of 3,4-dinitrothiophene with diethylamine, and arylmethylmagnesium chlorides in THF at 0°C furnished good yields of (E,E,E)-1,6-diaryl-3-nitro-1,3,5-hexatrienes. To explain the formation of the hexatrienes, a mechanism is advanced which involves, in particular, tautomerisation of the intermediate 1,6-diaryl-3,4-dinitro-2,4-hexadienes followed by base-induced elimination of nitrous acid. The electrocyclic disrotatory conversion of the hexatrienes into the corresponding 5,6-diaryl-2-nitro-1,3-cyclohexadienes was analysed by 1H NMR spectroscopy and exploited for the high-yielding synthesis of 1,2-diaryl-4-nitrobenzenes employing, as oxidants, either DDQ or iodine in the presence of cyclohexene oxide as HI scavenger.

Synthetic exploitation of the ring-opening of 3,4-dinitrothiophene. Part 7. Access to disubstituted 1,2,5-oxadiazole-2-oxides and 2-phenyl-2H-1,2,3-triazole-1-oxides☆

Abstract 1,4-Dialkyl- and 1,4-diaryl-2,3-bis(hydroxyimino)butanes 7, from reduction of the corresponding 1,4-disubstituted 2,3-dinitro-1,3-butadienes 2, are transformed with satisfactory yields into 3,4-disubstituted 1,2,5-oxadiazole-2-oxide 5 and 4,5-disubstituted 2-phenyl-2H-1,2,3-triazole-1-oxides 6. Dinitrobutadienes 2 are obtained from the reaction of 3,4-dinitrothiophene with diethylamine and subsequent treatment of the ensuing bis(diethylamino)butadiene 1 with Grignard reagents; thus the overall transformation represents a novel approach to 1,2,5-oxadiazole and 1,2,3-triazole systems via a ring-opening ring-closure strategy.