A Novel Synthesis of Some 1,4‐Phenylene‐bis‐heterocyclic Derivatives and of Some Pyran, Pyrano[2,3‐c]pyrazole, and Pyrano[2,3‐d]pyrimidine Derivatives [1]

Abstract

in Wiley Online Library (wileyonlinelibrary.com).p-Diacetyl benzene 1 undergoes bromination to afford p-bromoacetyl phenacyl bromide 2. Compound 2 reacts with twofold excess of malononitrile to afford 2-{2-[4-(3,3-Dicyanopropionyl)-phenyl]-2-oxo-ethyl}malononitrile 3. Compound 3 could be cyclized to afford the 1,4-phenylene-bis-furan derivative 4. Compound 3 reacts also with a twofold excess of hydrazine hydrate and phenyl hydrazine under dry conditions at RT to afford the bis-pyrazole derivatives 5a,b, respectively. The reaction of 5a,b with the same reagents in refluxing dioxane afforded the bis-pyrazolopyridazine derivatives 7a,b, respectively. The azo coupling of compound 3 with arene diazonium salts afforded the bis-pyrazole derivatives 9a-c. The β-keto esters 10a,b react with benzaldehyde and malononitrile in a one pot synthesis to afford the pyran derivatives 11a,b. These latter compounds react with hydrazine hydrate and urea derivatives to afford the pyrano[2,3-c]pyrazoles 15a,b and the pyrano[2,3-d]pyrimidine derivatives 17a,b, respectively.

3‐(3,5‐Dimethyl‐1H‐Pyrazol‐1‐yl)‐3‐Oxopropanenitrile as Precursor for Some New Mono‐Heterocyclic and Bis‐Heterocyclic Compounds

“…In the recent years, attention has been increasingly paid to the synthesis of novel mono‐heterocyclic and bis‐heterocyclic derivatives expected to exhibit various biological activities . In the light of these data and in continuation of our program, we have recently reported the synthesis of some new bis‐heterocyclic compounds of biological interest . Because of the increasing demand on such compounds, it was decided to synthesize a new group of functionally substituted bis‐chromenes and bis‐thiazole derivatives.…”

A new direction in the alkylation of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with active methylene reagents

“…All synthesized compounds ( 6 , 7 , 15 , 17 , 19 , 21 ) are known compounds and have been characterized in detail in the literature . Therefore, their structures were confirmed only by nuclear magnetic resonance (NMR) spectroscopy.…”

“…In a round‐bottomed flask, 0.8 g (0.00315 mol) of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4 H ‐pyran‐3‐carbonitrile and 0.42 g (0.032 mol) of acetoacetate were placed, dissolved in CHCl 3 , and stirred . After that, 7 mol% piperazine hydrate was added to the reaction mixture, which was refluxed for 8 h. Then the resultant reaction mixture was poured into a glass beaker.…”

“…It is known from the literature that substituted pyrans show antitumor, antibacterial, antiviral, antispasmodic, antifungal, and anti‐inflammatory properties . According to numerous published works, a convenient synthesis route to 4 H ‐pyrans is based on the Michael reaction of benzylidenemalononitriles with active methylene compounds under various conditions (Scheme ) …”

Synthesis of Some Novel 1,4‐Phenylene‐bis‐thiazolyl Derivatives and Their Anti‐hypertensive α‐blocking Activity Screening

“…Within the frame of this program we have recently reported many syntheses of several novel bisheterocyclic compounds [4][5][6].…”