Spiro Heterocycles Research Articles

Synthesis, Characterization and DPPH Scavenging Assay of Isatin Related Spiroheterocyclic Compounds

Isatin is synthetically a versatile substrate that can be used for the synthesis of large variety of heterocyclic compounds. 5-substituted isatins were treated with 2-amino-5-chlorobenzo phenone to form Schiff’s bases. Spirothiozolidin-4-ones and 5’-methyl-spiro-4-thiazolidiones were synthesized Schiff’s bases of isatins by treating with thioglycolic acid and thiolactic acid, respectively in the presence of 1,4-dioxane and anhydrous zinc chloride. The structures of the synthesized compounds were characterized by elemental and spectral analysis. These compounds were screened for their antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl method. Compound A02 found to possess potent antioxidant activity compared to the standards ascorbic acid and butylated hydroxytoluene.

ChemInform Abstract: Review of Synthesis and Various Biological Activities of Spiro Heterocyclic Compounds Comprising Oxindole and Pyrrolidine Moities

AbstractReview: 40 refs.

An Efficient Four‐component Reaction for the Synthesis of Spiroheterocyclic Compounds

A series of 6‐amino‐8‐aryl‐3,4‐dihydro‐1H‐spiro[naphthalene‐2,2'‐[1,3] dioxolane]‐5,7‐dicarbonitrile and 8‐arylidene‐4‐aryl‐7,8‐dihydro‐5H‐spiro[quinazoline‐6,2'‐[1,3] dioxolan]‐2‐amine derivatives have been synthesized from the reactions of 1,4‐dioxaspiro[4.5] decan‐8‐one, aromatic aldehydes, and malononitrile (or guanidine carbonate) under different conditions with high yields. In this research, it was found the DBU–THF was efficient reaction condition for obtaining 6‐amino‐8‐aryl‐3,4‐dihydro‐1H‐spiro[naphthalene‐2,2'‐[1,3]dioxolane]‐5,7‐dicarbonitrile derivatives, while 95% EtOH and NaOH was the preferred condition for the synthesis of 8‐rylidene‐4‐aryl‐7,8‐dihydro‐5H‐spiro[quinazoline‐6,2'‐[1,3]dioxolan]‐2‐amine derivatives. To the best of our knowledge, these Spiroheterocycles were first reported in our research. The other advantages of this process were short‐reaction time, wide scope substrates, and simple set‐up.

ChemInform Abstract: Hauser—Kraus Annulation of Phthalides with Nitroalkenes for the Synthesis of Fused and Spiro Heterocycles.

AbstractA Hauser—Kraus annulation of sulfonylphthalides with conjugated nitro alkenes furnishes naphthoquinones in moderate yields.

Bifunctional Heterocyclic Spiro Derivatives for Organic Optoelectronic Devices.

A series of heterocyclic spiro derivatives has been successfully synthesized and characterized by photophysical and electrochemical studies. Taking advantage of their excellent hole-transporting properties, highly efficient small-molecular organic photovoltaic devices based on these heterocyclic compounds as donors with very low dopant concentrations have been prepared; particularly, a high open-circuit voltage of up to 1.10 V and a power conversion efficiency of up to 5.12% have been realized. In addition, most of these heterocyclic spiro derivatives are found to be highly emissive in solutions with photoluminescence quantum yields of up to 0.91, and high-performance deep-blue-emitting organic light-emitting diodes (OLEDs) have been achieved. Such devices exhibit a stable deep blue emission with CIE coordinates of (0.16, 0.04) and high external quantum efficiencies of up to 4.7%, which is one of the best values among the reported OLEDs with CIEy < 0.08.

Gold/Lewis Acid Catalyzed Cycloisomerization/Diastereoselective [3 + 2] Cycloaddition Cascade: Synthesis of Diverse Nitrogen-Containing Spiro Heterocycles

A novel early and late transition-metal relay catalysis has been developed by combining a gold-catalyzed cycloisomerization and a Yb(OTf)3-catalyzed diastereoselective [3 + 2] cycloaddition with aziridines in a selective C-C bond cleavage mode. Various biologically significant complex nitrogen-containing spiro heterocycles were rapidly constructed from readily available starting materials under mild conditions.

Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro‐1,2‐Diazepinones by NHC‐Catalyzed [3+4] Annulation Reactions

AbstractA strategy for the NHC‐catalyzed asymmetric synthesis of spirobenzazepinones, spiro‐1,2‐diazepinones, and spiro‐1,2‐oxazepinones has been developed via [3+4]‐cycloaddition reactions of isatin‐derived enals (3C component) with in‐situ‐generated aza‐o‐quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven‐membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all‐carbon spiro stereocenter is generated.

Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro-1,2-Diazepinones by NHC-Catalyzed [3+4] Annulation Reactions.

A strategy for the NHC-catalyzed asymmetric synthesis of spirobenzazepinones, spiro-1,2-diazepinones, and spiro-1,2-oxazepinones has been developed via [3+4]-cycloaddition reactions of isatin-derived enals (3C component) with in-situ-generated aza-o-quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven-membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all-carbon spiro stereocenter is generated.

Regioselectivity and regiospecificity of benzoxazinone (2-isopropyl-4H-3,1-benzoxazinone) derivatives toward nitrogen nucleophiles and evaluation of antimicrobial activity

ABSTRACTA novel group of 6-iodoquinazolin-4(3H)-one derivatives was prepared. The reaction of the benzoxazinone 3 with various nitrogen nucleophiles such as formamide and hydrazine hydrate and also the reaction of the isopropylquinazolinone 4 with hydrazonyl chloride have been shown to proceed with a high degree of regioselectivity at C(2). Spiro heterocycles have been found to play fundamental roles in biological processes and have exhibited diversified biological activity and pharmacological and therapeutical properties; thus reaction of acetohydrazides 10a–c afforded the spiro compounds 11a–c. The acetohydrazide derivative 7 reacted with carbon electrophiles such as acetylacetone, ethyl acetoacetate, acid chlorides, and benzaldehyde to give some interesting heterocyclic compounds 12–16, respectively. The structures of all the synthesized compounds were inferred by infrared, 1H NMR, and mass spectra as well as elemental analyses. The antimicrobial activities of some of the synthesized products were preliminarily evaluated.

Hauser–Kraus Annulation of Phthalides with Nitroalkenes for the Synthesis of Fused and Spiro Heterocycles

Hauser–Kraus annulation of sulfonylphthalides with simple conjugated nitroalkenes follows the expected pathway to furnish naphthoquinones in moderate yields. However, a strategic variation of this reaction by employing nitroalkenes bearing an additional nucleophilic site results in [4+4] annulation leading to complex fused and spiro heterocycles in high yields with high selectivity through a cascade process involving Michael addition, Dieckmann cyclization, and a series of eliminations and rearrangements.

Stereo-, Regio-, and Chemoselective [3 + 2]-Cycloaddition of (2E,4E)-Ethyl 5-(Phenylsulfonyl)penta-2,4-dienoate with Various Azomethine Ylides, Nitrones, and Nitrile Oxides: Synthesis of Pyrrolidine, Isoxazolidine, and Isoxazoline Derivatives and a Computational Study

One-pot chemo-, regio-, and stereoselective synthesis of series of heterocyclic and spiroheterocyclic compounds was accomplished through mono- and bis[3 + 2]-cycloaddition reactions of (2E,4E)-ethyl 5-(phenylsulfonyl)penta-2,4-dienoate as a dipolarophile with azomethine ylides, nitrones, and nitrile oxides in good yields. The structures of the products were established by spectroscopic techniques as well as by single-crystal XRD study, and DFT calculations were performed to further understand the mechanism of this [3 + 2]-cycloaddition reaction.

Synthesis and Biological Activities Evaluation of New Spiro Heterocycles Containing 1,2,4-Triazole, Piperidine and Sulfonamide Moieties

Synthesis and Biological Activities Evaluation of New Spiro Heterocycles Containing 1,2,4-Triazole, Piperidine and Sulfonamide Moieties

ChemInform Abstract: Enantioselective Synthesis of Spiro[1,3‐indanedione‐tetrahydrothiophene]s by Organocatalytic Sulfa‐Michael/Michael Domino Reaction.

The organocatalytic asymmetric domino reaction between 2-arylidene-1,3-indanediones and 4-mercapto-2-butenoates for the construction of chiral spiro[indane-1,3-dione–tetrahydrothiophene] skeletons was developed. In the presence of a tertiary amine–thiourea organocatalyst, a series of 2-arylidene-1,3-indanediones reacted with tert-butyl 4-mercapto-2-butenoate smoothly to furnish chiral spiro heterocycles in good yields (75–99 %) with high enantioselectivities (89–99 % ee) and diastereoselectivities (75.4:24.6 to 97.1:2.9 dr). Notably, functionalized chiral spiro heterocycles were also built in one pot through an aldol condensation/sulfa-Michael/Michael domino reaction in similarly high yields with high asymmetric induction.

Synthesis and Regioselective Reaction of Some Unsymmetrical Heterocyclic Chalcone Derivatives and Spiro Heterocyclic Compounds as Antibacterial Agents.

A number of novel heterocyclic chalcone derivatives can be synthesized by thermal and microwave tools. Treatment of 4-(4-Acetylamino- and/or 4-bromo-phenyl)-4-oxobut-2-enoic acids with hydrogen peroxide in alkaline medium were afforded oxirane derivatives 2. Reaction of the epoxide 2 with 2-amino-5-aryl-1,3,4-thiadiazole derivatives yielded chalcone of imidazo[2,1-b]thiadiazole derivative 4 via two thermal routes. In one pot reaction of 4-bromoacetophenone, diethyloxalate, and 2-amino-5-aryl-1,3,4-thiadiazole derivatives in MW irradiation (W 250 and T 150 °C) under eco-friendly conditions afforded an unsuitable yield of the desired chalcone 4d. The chalcone derivatives 4 were used as a key starting material to synthesize some new spiroheterocyclic compounds via Michael and aza-Michael adducts. The chalcone 4f was similar to the aryl-oxo-vinylamide derivatives for the inhibition of tyrosine kinase and cancer cell growth. The electron-withdrawing substituents, such as halogens, and 2-amino-1,3,4-thiadiazole moeity decreasing the electron density, thereby decreasing the energy of HOMO, and the presence of imidazothiadiazole moiety should improve the antibacterial activity. Thus, the newly synthesized compounds were evaluated for their anti-bacterial activity against (ATCC 25923), (ATCC 10987), (ATCC 274,) and (SM514). The structure of the newly synthesized compounds was confirmed by elemental analysis and spectroscopic data.

Synthesis of Some New Fused and Spiro Heterocyclic Compounds under Phase Transfer Catalysis (PTC) Conditions

Synthesis of Some New Fused and Spiro Heterocyclic Compounds under Phase Transfer Catalysis (PTC) Conditions

ChemInform Abstract: Double Michael Adducts: Source for Spiro Heterocycles.

ChemInform Abstract: Double Michael Adducts: Source for Spiro Heterocycles.

Enantioselective Synthesis of Spiro[1,3‐­indanedione–tetrahydrothiophene]s by ­Organocatalytic Sulfa‐Michael/Michael Domino Reaction

AbstractThe organocatalytic asymmetric domino reaction between 2‐arylidene‐1,3‐indanediones and 4‐mercapto‐2‐butenoates for the construction of chiral spiro[indane‐1,3‐dione–tetrahydrothiophene] skeletons was developed. In the presence of a tertiary amine–thiourea organocatalyst, a series of 2‐arylidene‐1,3‐indanediones reacted with tert‐butyl 4‐mercapto‐2‐butenoate smoothly to furnish chiral spiro heterocycles in good yields (75–99 %) with high enantioselectivities (89–99 % ee) and diastereoselectivities (75.4:24.6 to 97.1:2.9 dr). Notably, functionalized chiral spiro heterocycles were also built in one pot through an aldol condensation/sulfa‐Michael/Michael domino reaction in similarly high yields with high asymmetric induction.

ChemInform Abstract: Hypervalent‐Iodine‐Mediated Cascade Annulation of Diarylalkynes Forming Spiro Heterocycles under Metal‐Free Conditions.

AbstractThis unprecedented process involves two sequential C—N/C—O bond formations and insertion of a carbonyl oxygen in a convenient one‐pot process to give a wide variety of spiro heterocycles.

ChemInform Abstract: Synthesis of Spiro Compounds as Medicinal Agents; New Opportunities for Drug Design and Discovery. Part I: A Review

AbstractReview: 109 refs.

Synthesis, molecular structure and spectroscopic investigations of novel fluorinated spiro heterocycles.

This paper describes an efficient and regioselective method for the synthesis of novel fluorinated spiro-heterocycles in excellent yield by cascade [5+1] double Michael addition reactions. The compounds 7,11-bis(4-fluorophenyl)-2,4-dimethyl- 2,4-diazaspiro[5.5] undecane-1,3,5,9-tetraone (3a) and 2,4-dimethyl-7,11-bis (4-(trifluoromethyl)phenyl)-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone (3b) were characterized by single-crystal X-ray diffraction, FT-IR and NMR techniques. The optimized geometrical parameters, infrared vibrational frequencies and NMR chemical shifts of the studied compounds have also been calculated using the density functional theory (DFT) method, using Becke-3-Lee-Yang-Parr functional and the 6-311G(d,p) basis set. There is good agreement between the experimentally determined structural parameters, vibrational frequencies and NMR chemical shifts of the studied compounds and those predicted theoretically. The calculated natural atomic charges using NBO method showed higher polarity of 3a compared to 3b.The calculated electronic spectra are also discussed based on the TD-DFT calculations.