Spiroheterocyclic Systems Research Articles

Reaction of Pyrrolobenzothiazines with Schiff Bases and Carbodiimides: Approach to Angular 6/5/5/5-Tetracyclic Spiroheterocycles.

1H-Pyrrole-2,3-diones, fused at [e]-side with a heterocycle, are suitable platforms for the synthesis of various angular polycyclic alkaloid-like spiroheterocycles. Recently discovered sulfur-containing [e]-fused 1H-pyrrole-2,3-diones (aroylpyrrolobenzothiazinetriones) tend to exhibit unusual reactivity. Based on these peculiar representatives of [e]-fused 1H-pyrrole-2,3-diones, we have developed an approach to an unprecedented 6/5/5/5-tetracyclic alkaloid-like spiroheterocyclic system of benzo[d]pyrrolo[3',4':2,3]pyrrolo[2,1-b]thiazole via their reaction with Schiff bases and carbodiimides. The experimental results have been supplemented with DFT computational studies. The synthesized alkaloid-like 6/5/5/5-tetracyclic compounds have been tested for their biotechnological potential as growth stimulants in the green algae Chlorella vulgaris.

Modified 7-Chloro-11H-indeno[1,2-b]quinoxaline Heterocyclic System for Biological Activities

Recent advances in functionalized organic Spiro heterocyclic compounds composed of nitrogen bonded five- and six-membered rings have been made, establishing them as a synthetic target in organic-based biomedical applications. In this work, we report a synthesis of spirocyclic compounds under a one-pot reaction using 1,3-dipolar cycloaddition in a regio and diastereoselective manner. The higher atomic economy with higher yield (95%) and regio and stereoselectivity were achieved by a multi-component reaction of L-proline (1), Indenoquinoxaline (2), and the dipolarophile of malononitrile (3) solvents followed by reflux conditions. The reaction intermediate comprised azomethineylides derived from reactive primary amines, and the spiro derivatives were synthesized up to a ≈ 95% yield. The structural and characteristic chemical components of the as-prepared Spiro compounds were characterized by 1H-NMR, FTIR, and Mass spectroscopy. The functionalized spiro-pyrrolizidines were found to be effective for biological uses by considering their in vitro screening and antimicrobial impacts. Spiro constituents were found to be much more effective for Gram-positive bacteria due to the stronger lipophilic character of the molecules, and they resulted feasible membrane permeation in a biological system. Based on the planarity geometry of the Spiro pyrrolizidines, meta-substitution possesses steric hindrance and hence shows less effectiveness compared to para-substitution on the same nucleus, which shows a marginal steric effect. The biological studies showed that the derived spiro heterocyclic systems have an inhibitory effect of 50%.

Enantiomeric pairs of meroterpenoids with 11/5/6 spiro-heterocyclic systems from Hypericum kouytchense

Undescribed enantiomeric pairs of acylphloroglucinol related meroterpenoids with 11/5/6 spiro-heterocyclic systems were isolated from Hypericum kouytchense.

Synthesis and dynamic NMR study of spiroheterocycles containing a 1,2,4-triazolidine moiety

A one-pot synthesis of spiro-heterocyclic systems containing a 1,2,4-triazolidine moiety via 1,3-dipolar cycloaddition reaction of azomethine ylides (generated in situ from α-amino acids and ninhydrin) with diisopropyl azodicarboxylate in 50% aqueous MeOH at room temperature, is described. The structure of a typical product was confirmed by X-ray crystallography. The 1H NMR spectra of diisopropyl 1,3-dioxo-1,3-dihydrospiro[indene-2,3′-[1,2,4]triazolidine]-1′,2′-dicarboxylate exhibited dynamic NMR effects, which were attributed to the fast positional change of the ester groups and their interaction with N–H as well as with methylene protons, and restricted bond rotation of the carbamate groups. The calculated free-energy of activation (ΔG#) for these dynamic processes are 64 ± 2 kJ mol−1 and 55 ± 2 kJ mol−1, respectively.

Microwave Assisted Synthesis of Spiro Heterocyclic Systems: A Review

Microwave Assisted Synthesis of Spiro Heterocyclic Systems: A Review

ChemInform Abstract: Copper(I) Catalyzed Diastereoselective Multicomponent Synthesis of Spiroindolo‐pyrrolidines/‐imidazolidines/‐triazolidines from Diazoamides via Azomethine Ylides.

AbstractThe novel method to synthesize highly substituted spiroindolo‐pyrrolidines/‐imidazolidines/‐triazolidines is efficiently catalyzed by Cu(I)TC.

An unexpected route for the synthesis of a new spiroheterocyclic system from ninhydrin

The reaction of ninhydrin with amines leads to the formation of Ruhemann’s purple. This study presents the synthesis of Ruhemann’s purple and a new benzo-fused spiroheterocyclic system by the reaction between ninhydrin and phenylethylamine. The structure was established using spectroscopic data and X-ray crystal structure analysis.

Efficient methods for the synthesis of spiroheterocyclic systems based on 4,4,6-trimethyl-4H-pyrrolo[3,2,1-ij]quinoline-1,2-diones

Cyclocondensation of 4H-pyrrolo[3,2,1-ij]quinoline-1,2-diones with some 1,2- and 1,3-dinucleophiles, their three-component cyclocondensations with arylamines and 2-mercapto-acetic acid, as well as with malononitrile and various methylene active carbonyl compounds lead to new heterocyclic systems: spiro[imidazolidine-2,1’-pyrrolo[3,2,1-ij]quinoline], spiro[1,3-dioxolane-2,1’-pyrrolo[3,2,1-ij]quinoline], spiro[1,3-benzothiazole-2,1’-pyrro- lo[3,2,1-ij]quinoline], spiro[β-carboline-1,1’-pyrrolo[3,2,1-ij]quinoline], spiro[3,1-benzoxazine-2,1’-pyrrolo[3,2,1-ij]quinoline], spiro[pyrrolo[3,2,1-ij]quinoline-1,2’-quinazoline], spiro[pyrrolo[3,2,1-ij]quinoline-1,2’-[1,3]thiazolidine], spiro[pyran-4,1’-pyrrolo[3,2,1-ij]- quinoline], spiro[chromene-4,1’-pyrrolo[3,2,1-ij]quinoline], spiro[pyrano[4,3-b]pyran-4,1’- pyrrolo[3,2,1-ij]quinoline], spiro[pyrano[3,2-c]chromene-4,1’-pyrrolo[3,2,1-ij]quinoline], and spiro[pyrano[2,3-c]pyrazole-4,1’-pyrrolo[3,2,1-ij]quinoline].

Preparation of Spiro[Benzopyran-Isoxazoles] from the Condensation–Cyclization of Oxime 1,4-Dianions with Select Coumarins

A representative spiro[benzopyran-isoxazole], 3′-(3,4-dimethoxyphenyl)-N,N-diethyl-4-methyl-4′H-spiro[2H-1-benzopyran-2,5′-isoxazol]-7-amine 3a, was submitted for single crystal X-ray analysis. It has been prepared by the condensation–cyclization of dilithiated C(α),O-3′,4′-dimethoxyacetophenone oxime with a substituted coumarin, 7-(diethylamino)-4-methyl-2H-1-benzopyran-2-one. This results from the 1,2-carbonyl addition, Claisen type, of the dilithiated oxime with this coumarin ester carbonyl to afford C-acylated intermediates that were not isolated, but were acid cyclized to the spiro[benzopyran-isoxazoles], a new spiro heterocyclic system. There was no evidence for Michael-type 1,4-addition found during this initial investigation. An indication that the experimental multiple anion procedure is general, has been the preparation of two additional spiro(benzopyran-isoxazoles) 3b and 3c. Crystals of C24H28N2O4 3a are triclinic, $$p\bar{1}$$ , a = 9.161(2) A, b = 9.716(2) A, c = 12.869(3) A, α = 75.84(3)°, β = 81.03(3)°, γ = 73.96(3)°, Z = 2, V = 1062.5(4) A3, R 1 = 0.0539 and wR 2 = 0.1366 for reflections with I > 2σ(I). X-ray crystal analysis confirmed the structure of 3′-(3,4-dimethoxyphenyl)-N,N-diethyl-4-methyl-4′H-spiro(2H-1-benzopyran-2,5′-isoxazol)-7-amine prepared by the condensation–cyclization of dilithiated C(α),O-3′,4′-dimethoxyacetophenone oxime with a substituted coumarin, 7-(diethylamino)-4-methyl-2H-1-benzopyran-2-one.

ChemInform Abstract: Microwave‐Induced Solvent‐Free Synthesis and Antifungal Screening of Novel Spiro Heterocyclic Systems Containing 3,5‐Diphenyl‐7H‐thiazolo[3,2‐a]pyrimidine and Indolin‐2‐one.

AbstractA facile, environmentally benign and economic synthesis of spiro compounds (V) (7 examples) incorporating two biologically important heterocycles is described.

An Efficient Synthesis of Some New Azaspirocycloalkane Derivatives from 1-anilinocycloalkanecarboxamide

1-anilinocyclohexanecarboxamides 2a-c were found to be a versatile precursors for the synthesis of five-, six- and seven-membered ring spiroheterocycles compounds 3-14. A general high yielding protocol for the synthesis of many functionalized spiro heterocyclic systems was presented.

Five-membered 2,3-dioxo heterocycles: XCVII. Reaction of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones with Fischer’s base

Abstract —3-Aroylpyrrolo[1,2- a ]quinoxaline-1,2,4(5 H )-triones reacted with 1,3,3-trimethyl-2-methylidene-2,3-dihydro-1 H -indole (Fischer’s base) to give (2 Z )-1-aryl-2-[3-oxo-3,4-dihydroquinoxalin-2(1 H )-ylidene]-5-(1,3,3-trimethyl-2,3-dihydro-1 H -indol-2-ylidene)pentane-1,3,4-triones. * For communication XCVI, see [1]. Substituted 4-acyl-1 H -pyrrole-2,3-diones, including those fused by the [ e ] side to aza heterocycles, readily react with binucleophiles to produce a variety of fused heterocyclic and spiro-heterocyclic systems [2–4]. We previously studied reactions of 4-acyl-1 H -pyrrole-2,3-diones fused to quinoxalin-2-one fragment, 3-aroylpyr-rolo[1,2- a ]quinoxaline-1,2,4(5 H )-triones, with primary enamines. The reactions of pyrroloquinoxalinetriones with N -alkyl-substituted dimedone imines involved successive addition of the β-CH and NH groups in the enamine fragment of the latter (enamine tautomer) to the C 3a and C 2 atoms of pyrroloquinoxalinetrione, respectively, to give bridged 3,10,13-triazapentacyclo-[10.7.1.0

Microwave-Induced Solvent-Free Synthesis and Antifungal Screening of Novel Spiro Heterocyclic Systems Containing 3,5-Diphenyl-7H-thiazolo[3,2-a]pyrimidine and Indolin-2-one

A microwave-induced technique has been developed for the synthesis of a series of novel spiro indoline-based heterocycles (7a–g) at atmospheric pressure in an open vessel using an environmentally benign procedure. This rapid method produces pure products in good yields within a few minutes in comparison to the conventional procedure developed for the synthesis of these heterocycles. The synthesized compounds have been screened in vitro for antifungal activity against two fungal strains (i.e., Aspergillus niger and Aspergillus flavus). All compounds have shown significant activity against these pathogens. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.]

Interaction of spiro-heterocyclic oxindole system with sodium diformylimide

New functionalized condensed benzazoles have been synthesized based on isatin, 3,4-diaminofurazane, and sodium diformylimide.

The chameleon-like behaviour of 3-amino-1,2,4-triazole in the Biginelli reaction: unexpected formation of a novel spiroheterocyclic system

A novel Biginelli-like assembly of 3-amino-1,2,4-triazole with methyl acetoacetate and salicylaldehyde has been developed to enable easy access to spiro{[1]benzopyran-2,7′-[1,2,4]triazolo[1,5- a]pyrimidine} compounds as representatives of a new class of spiro-fused heterocycles. A three-component condensation mechanism is proposed and discussed.

ChemInform Abstract: Novel Synthesis of Some Spiro Heterocycles Derived from 3-Hydroxy-3(2-oxocyclohexyl)indolin-2-one.

Abstract The reaction of 3-hydroxy-3(2-oxocyclohexyl)indolin-2-one 1 with some active methylene, bidentates, phenylisocyanate, phenylisothiocyanate, carbon disulfide, benzaldehyde, ketoketene S,S-acetal, cyanoketene S,S-acetal, active halo compounds or benzylidenemalononitrile affords a series of new spiro heterocyclic systems.

Electrophilic Substitution Reaction of Indole: Part XXII-Synthesis of a Novel Spiro Heterocyclic System

The reaction of indole with acetone in the presence of mineral/Lewis acid continues to be a fascinating area for investigation since 1913, specially due to the instability of the indolyl carbinol being generated in situ. We report here the synthesis of a novel spiro heterocyclic system obtained during the study of this reaction using BF3.Et20.

Highly Efficient and Site-Selective [3 + 2] Cycloaddition of Carbene-Derived Ambident Dipoles with Ketenes for a Straightforward Synthesis of Spiro-Pyrrolidones

The [3 + 2] cycloaddition reaction of 2-arylthiocarbamoyl benzimidazolium, -imidazolinium, and -triazolium inner salts (the ambident C-C-N and C-C-S 1,3-dipoles derived from carbenes) with ketenes proceeded efficiently in a highly site-selective manner to produce the C-C-N cycloaddition products benzimidazoline-, imidazolidine-, or triazoline spiro-pyrrolidones in 58-93% yields. Theoretical calculation suggests a stepwise mechanism for the reaction and indicates that the C-C-N cycloaddition of the dipoles with ketenes is both a dynamically and thermodynamically favored reaction pathway. Their easy availability, high reactivity, and reaction selectivity render the benzimidazolium, -imidazolinium, and -triazolium inner salts powerful and versatile 1,3-dipoles in the construction of novel spiro heterocyclic systems, which are not easily accessible by other methods.

Synthesis of Spiroheterocyclic Systems from Barbituric Acids and N,N‐Disubstituted o‐Aminobenzaldehydes.

Reactions of barbituric, 1,3-dimethylbarbituric, and 2-thiobarbituric acids with 2-(1-pyrrolidinyl)benzaldehyde, its 6- and 7-membered homologs, and 4-phenylpiperazine and morpholine analogs lead to formation of fused systems with a spirocyclic 2,4,6-trioxopyrimidine fragment. The process involves intermediate formation of labile 5-arylmethylidenebarbituric acids which exhibit t-amino effect and undergo spontaneous isomerization to give the final products. The observed spirocyclizations are characterized by an anomalously high rate.

Synthesis of Spiroheterocyclic Systems from Barbituric Acids and N,N-Disubstituted o-Aminobenzaldehydes

Reactions of barbituric, 1,3-dimethylbarbituric, and 2-thiobarbituric acids with 2-(1-pyrrolidinyl)benzaldehyde, its 6- and 7-membered homologs, and 4-phenylpiperazine and morpholine analogs lead to formation of fused systems with a spirocyclic 2,4,6-trioxopyrimidine fragment. The process involves intermediate formation of labile 5-arylmethylidenebarbituric acids which exhibit t-amino effect and undergo spontaneous isomerization to give the final products. The observed spirocyclizations are characterized by an anomalously high rate.