Schutzgruppen zur Synthese von Diaza‐cyclophanen nach dem „Rigid‐Group‐Principle”︁

Abstract

4,4-Dimethyl-l,2-bis(4-methylphenyl)-3,5-pyr~lidindion (4), 12-Bis(4-methylphenyl)perhydro-3,6-pyridazindion (5) und 1 ,2-Bis(4-methylphenyl)perhydro-3,7-diazepindion (6) wurden durch Kondensation von p-Hydrazotoluol mit den entsprechenden Dicarbonsiiuredichloriden dargestellt und durch Photobromierung in die Brommethylderivate 7 -9 GbergeTUhrt. Die Eignung von 7 -9 als Vorstufen fiir die Synthese von 2-Thia-IO,ll-diaza[3.2]paracyclophan-10-en (2) und 2,5-Dithia-l3,14-diaza[6.2]paracyclophan-13-en (3) wurde gepriift. Die Darstellung von 2 gelang unabhlngig von der Ringgriik und Konformation von 7-9 nicht.3 wird dagegen in allen Fallen glatt gebildet, wobei sich der Dimethylmalonylrest wegen der guten Zugiinglichkeit, Stabilitiit und leichten Abspaltbarkeit im alkalischen Milieu besonders be- gelang bisher nur die Synthese des N,N-Phthaloylderivats des Paraisomeren 2 durch Ausnutzen eines ,,Caesiumeffekts" ' ) bei der Cyclisierung nach Schema 1 ' ). bis(4-methylphenyl)perhydro-3,7-diazepin (6) have been prepared by condensation of p-hydrazotoluene with the appropriate dicarbonyl dichlorides and then converted into the corresponding bis(bromomethy1) derivatives 7 -9 by photobromination. 7 -9 have been tested as starting compounds for the synthesis of 2-thia-lO,ll-diaza[3.2]paracyclophan-lO-ene (2) and 2,5dithia-13,14-diaza[6.2]paracyclophan-l3-ene (3). In no case 2 has been obtained, independent of the ring size and conformation of 7-9. However, 3 was readily formed from all precursors; the dimethylmalonyl moiety proved to be convenient as a protecting group because of its ease of preparation, its stability, and its facile cleavage by alkali.

Use of Electrochemistry in the Synthesis of Heterocyclic Structures

“…The conventional approach to pyrazolidin-3,5-diones employs an activated malonic acid derivative and an N,N'-diarylhydrazine as the substrates. 99 Although this approach is effective for the construction of simple pyrazolidin-3,5-diones, this approach has two major drawbacks. First, most hydrazine derivatives are highly carcinogenic.…”

“…Employing easily accessible and inexpensive starting materials, a broad substitution pattern is tolerated and nonsymmetrical substrates can also be converted to give corresponding pyrazolidin-3,5-diones in yields up to 89%. The conventional approach to pyrazolidin-3,5-diones employs an activated malonic acid derivative and an N , N’ -diarylhydrazine as the substrates . Although this approach is effective for the construction of simple pyrazolidin-3,5-diones, this approach has two major drawbacks.…”

Synthesis of 4‐alkyl‐1,2‐diphenyl‐3,5‐dioxopyrazolidines possessing aryl methylsulfonyl and sulfonamide pharmacophores for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors

“…A group of 1-(4-methylsulfonylphenyl)-2-phenyl-4-alkyl-3,5-dioxopyrazolidines were synthesized using a modification of literature procedures [10][11][12] by the reaction sequence illustrated in Scheme 1. Accordingly, the acid catalyzed condensation of the nitrosobenzene compounds 5a-c with 4-(methylthio)aniline (6) afforded the respective 4-methylthioazobenzene products 7 a -c. Oxidation of the methylthio group (7a-c) using potassium peroxymonosulfate gave the corresponding methylsulfonyl derivatives (8a-c).…”

“…A group of 1,2-diphenyl-3,5-dioxopyrazolidines were prepared to investigate the effect of methylsulfonyl (11) and sulfonamido (15) substitution at the para-position of the N 1 -phenyl ring, in conjunction with a hydrogen, methyl or fluoro substituent (R 1 ) at the para-position of the N 2 -phenyl ring and a C-4 n-butyl, methyl or spirocyclopropyl substituent (R 2 ), on in vitro COX-1 and COX-2 inhibitory activities and COX-2 selectivity (see Table 1), and in vivo antiinflammatory and analgesic activities.…”

Zugang zu Pyrazolidin‐3,5‐dionen durch anodischen N‐N‐Bindungsaufbau

“…Der Ansatz für die Retrosynthese der Pyrazolidin-3,5dione basiert auf der Kombination einer aktivierten Malonsäure und eines N,N'-Diarylhydrazins. [5] Dieser Zugang scheint zwar einfach zu sein, hat aber zwei entscheidende Nachteile:E rstens sind die meisten Hydrazinderivate stark kanzerogen. [6] Daher sind besondere Sicherheitsbestimmungen erforderlich, und eine Übertragung auf einen grçßeren Maßstab ist problematisch.…”