Synthesis of Substituted Tricyclo[5.3.1.04,9]undecan‐2,6‐dione from 4,4‐Disubstituted Cyclohexanone Enamines and Methacryloyl Chloride

Morpholine enamines 4‐acetyl‐4‐methyl‐1‐morpholinocyclohexene 4a, 4‐acetyl‐4‐phenyl‐1‐morpholinocyclohexene 4b, and 4‐acetyl‐4‐isopropenyl‐1‐morpholinocyclohexene 4c react with methacryloyl chloride to give 1,7‐dimethyl‐4(N‐morpholino) tricyclo[5.3.1.0^4,9]undecan‐2,6‐dione 9a , 1‐phenyl‐7‐methyl‐4(N‐morpholino) tricyclo[5.3.1.0^4,9]undecan‐2,6‐dione 9b , and 1‐ispropenyl‐7‐methyl‐4(N‐morpholino) tricyclo[5.3.1.0^4,9]undecan‐2,6‐dione 9c respectively, along with the corresponding substituted adamandane‐2,4‐diones.     

Convenient synthesis and antitumor evaluation of some new 9-ethyl-3-(hetaryl)carbazoles

Abstract

In continuing our efforts to develop new potent anticancer candidates, a new series of 9-ethylcarbazoles carrying at position 3 various heterocyclic substituents such as 2-imino-2H-chromenes 5a–e, 2-oxo-2H-chromenes 6a–e, 3-imino-3H-benzo[f]chromene 8, 3-oxo-3H-benzo[f]chromene 9, 2-pyridones 11, 14, pyrazole 19, pyrimidine 23, pyrido[1,2-a]pyrimidine 27, 2H-pyran-2-one 30, and pyrano[2,3-d]pyrimidinetrione 34 were efficiently synthesized, characterized and evaluated for their in vitro antitumor activity. The mechanism for the synthesis of compounds was also discussed. Most of the synthesized compounds were displayed the considerable anticancer activities against three human tumor cells lines, in particular, colon carcinoma (HCT-116), hepatocellular carcinoma (HepG-2) and breast cancer (MCF-7). Compound 6d proves as most active molecule in this study with special effectiveness against the human HCT-116 and HepG-2 as its IC₅₀ values are 1.50, 0.90?μM, respectively, when doxorubicin is compared. Compound 34 was also found to have high activity against HepG-2, HCT-116 and moderate activity against MCF-7.     

Synthesis and reactions of 4H-3,1-benzoxazin-4-one derivative bearing pyrazolyl moiety as antimicrobial and antioxidant agents

Ring opening of 4-aryl-2-phenyloxazol-5-one 1 with 2-aminobenzoic acid in acetic acid and n-butanol gave compounds 2 and 3, respectively. The 4H-3,1-benzoxazin-4-one derivative 4 was synthesized by refluxing of compound 2 in acetic anhydride. Then it reacted with different nitrogen nucleophiles such as hydrazine hydrate, phenylhydrazine, cyclohexylamine, piperidine, ethylenediamine, ethanolamine, semicarbazide hydrochloride, cyanoacetohydrazide and methyl glycinate hydrochloride to give compounds 5–14 in order to study the behavior of these nucleophilic reagents on the performed ring system. All the structures of the newly prepared compounds were characterized by their IR, ¹H-, 13C-NMR and MS spectral data. Some of the synthesized compounds were screened for their antimicrobial and antioxidant activities. Compound 5 showed remarkable activity upon this screening.     

Synthesis of 1,4‐Diaryl‐piperazine‐2,5‐diones: New Behavior of N,N‐Dimethylformamide Dimethyl Acetal (DMFDMA)

Reactions of chloroacetamides (5) with N,N‐dimethylformamide dimethyl acetal gave 1,4‐diaryl‐piperazine‐2,5‐diones 11a–e in good yield, rather than 1,5‐diaryl‐3,7‐dimethoxy‐1H,5H‐[1,5]diazocine‐2,6‐diones (9a–e).     

Synthesis of Trichlorophenol Derivatives

An expedient three‐step procedure for the synthesis of trichlorophenol derivatives based on the acid‐catalyzed rearrangement of the bicyclic ketone precursors 6a–e in high overall yield is described. The bicyclic ketone precursors 6a–e were obtained from Diels–Alder cycloadducts of β‐substituted vinyl acetates with tetrachloro‐5,5‐dimethoxycyclopentadiene in two steps.     

Short,Convenient Preparative Procedures for 7-Isopropylidenenorbornane, 7-Isopropylidenenorbornene,and 7-Isopropylidenenorbornadiene

Short synthetic routes to the title compounds 1,–3, from readily available Diels-Alder adduct 5 of 6,6-dimethylfulvene and acrylonitrile are described.     

Enamine Rearrangement of Pyridinium Salts to Indole Ring: A Combined Experimental and Molecular Modeling Study

N‐Alkyl pyridinium ( II ) and N‐alkyl isoquinolinium salts V undergo cyclization reaction when heated with sodium bicarbonate to give the corresponding indolizine derivatives III and VIa , VIb , VIc , VId , VIe , respectively, which undergo ring opening and recyclization reactions when heated with aqueous sodium hydroxide to give the corresponding indole derivatives IV and IXa , IXb , IXc , IXd , IXe , respectively. Molecular modeling tools including Molecular Mechanics using Augmented MM3 parameters followed by geometry optimization calculations in MO‐G using PM3 parameters were performed to gain better understanding and more insights on the thermodynamic properties of the recyclization reactions of compounds IIa , IIb , IIc , IId , IIe , IIf , IIg to the corresponding IIIa , IIIb , IIIc , IIId , IIIe , IIIf , IIIg and IIIa , IIIb , IIIc , IIId , IIIe , IIIf , IIIg to the corresponding IVa , IVb , IVc , IVd , IVe , IVf , IVg . The results were in excellent agreement with the experimental data and hence were proven to be a good tool in explaining different yields % because of the steric and electronic effects of electron‐withdrawing groups on the reactivity of the pyridine ring for nucleophilic attack.     

Simplified Approach to the Uncatalyzed Knoevenagel Condensation and Michael Addition Reactions in Water using Microwave Irradiation

Use of microwave irradiation in the synthesis of arylidenemalononitrile and benzopyran derivatives in water without catalyst is a clean method with high yield.     

Recent Progress in the Chemistry of 2-Tosylacetonitrile

This review is a broad overview of the chemistry of 2-tosylacetonitrile, which considered as a very reactive synthetic compound. The synthetic methods are reported. The reactions of the title compound lead to the preparation of a variety of heterocyclic ring systems, such as five- and six-membered ring systems containing one, two, or three heteroatoms. The reaction mechanisms are discussed.