Cyclization of 1-benzyl-1,2-dihydro-2-(substituted methylene)quinolines to pyrrolo[1,2-a]quinoline derivatives

1-Alkyl-2-alkylthioquinolinium salts were prepared from 1-alkyl-2(1H)-quinolones via 1-alkyl-2(1H)-thioquinolones in two steps. Under mild conditions, the reaction of 1-alkyl-2-alkylthioquinolinium iodides with active methylene compounds in the presence of sodium hydride afforded 1-alkyl-1,2-dihydro-2-(substituted methylene)quinolines in good yields. The cyclization of 1-benzylquinolines using acetic anhydride produced the corresponding pyrrolo[1,2-a]quinoline derivatives.     

Base-free NIS promoted electrophilic cyclization of alkynes: an efficient synthesis of iodo substituted pyrano[4,3-b]quinolines

A simple and mild procedure for the synthesis of iodo substituted 1H-pyrano[4,3-b]quinolines has been achieved using NIS reagent in the absence of base from 2-alkynylquinoline-3-carboxaldehydes via intramolecular electrophilic cyclization onto alkynes in good to excellent yields in a short duration of time. The reactions proceeded smoothly in a normal solvent in aerobic atmosphere at room temperature. The presence of substituent at either quinoline or alkyne moieties did not show effect on reaction rate of cyclization. The palladium-catalyzed transformations of iodo group to C-C bond are also discussed.     

A Facile Synthesis of 5‐Phenyl‐Dibenzo[b,g][1,8]Napthyridines

The Vilsmeier Haack heterocyclization of 2‐aryl amino‐4‐phenyl quinolines quinoline yielded the hitherto unknown 5‐phenyl‐dibenzo[b,g][1,8]naphthyridines in quantitative yield. The synthesis of aryl amines was achieved by the action of anilines on 2‐chloro‐4‐phenyl quinoline, which in turn was sourced through the combes reaction of benzoyl acetanilides.     

[5C+1N]成环反应：吡啶-4(1H)酮类化合物的一种简便合成方法

用N,N-二甲基丙烯酰基二硫缩烯酮类化合物2与各种脂肪胺类化合物3在N,N-二甲基甲酰胺溶剂中60 ℃条件下,氮乙烯基发生分子内的亲核取代反应,通过[5C+1N]成环反应,合成了系列吡啶-4(1H)酮类化合物4,产率在75%~95%之间。     

Ethynyl ketene-S,S-acetals: the highly reactive electron-rich dienophiles and applications in the synthesis of 4-functionalized quinolines via a one-pot three-component reaction

An efficient synthetic method for 4-functionalized quinoline derivatives, 4-((1,3-dithian-2-ylidene)methyl)quinolines, has been developed. Mediated by trifluoromethanesulfonic acid, ethynyl ketene-S,S-acetals can react in a one-pot procedure with various arylamines and aldehydes under mild conditions to give the corresponding quinoline derivatives in good to high yields via a consecutive arylimine formation, regiospecific aza-Diels-Alder (Povarov) reaction, and reductive amination.     

Synthesis of Ethyl 2-Cyano-3-Methylthio-3'-Arylaminoacrylate From Low Nucleophilic Amine

The synthesis of ketene N,S-acetals has attracted a considerable attention as building blocks in organic synthesis, especially in the preparation of heterocycles^[1]. The addition reaction of ketene S,S-acetals with highly nucleophilic amines, such as alkylamines, can easily afford the corresponding ketene N,S-acetals, under gentle condition, which could be converted into conjugated ketene aminals by reaction with a second equivalent of the same or a different amine^[2,3]. However, this addition reaction with low nucleophilic amines, such as arylamine or heterocyclic amine, can hardly give the corresponding ketene N,S-acetals under gentle conditions. If under powerful condition,such as refluxing, the addition reaction affords a mixture of the N,S-acetals and conjugated ketene aminals^[4]. Recent studies showed that this addition reaction with low nucleophilic amines affords the corresponding ketene N,S-acetals in the presence of a catalyst^[5].     

Synthesis of poly-substituted pyrazolo[1,5-a]quinolines through one-pot two component cascade reaction

A diversity-oriented method for the synthesis of novel poly-substituted pyrazolo[1,5-a]quinolines has been developed on the basis of an S_NAr/Knoevenagel cyclization cascade reaction or an S_NAr/Dieckmann–Thorpe cyclization cascade reaction. The methods provide a variety of poly-substituted pyrazolo[1,5-a]quinolines bearing an amino, alkyl or aryl substituent at the 5-position. In addition, a diversity-oriented method for the synthesis of 2-substituted pyrazolo[1,5-a]quinolines from a readily available 2-[[(trifluoromethyl)sulfonyl]oxy]pyrazolo[1,5-a]quinoline has also been disclosed.     

InCl3‐Driven Regioselective Synthesis of Functionalized/Annulated Quinolines: Scope and Limitations

The efficient, regioselective synthesis of functionalized/annulated quinolines was achieved by the coupling of 2‐aminoaryl ketones with alkynes/active methylenes/α‐oxoketene dithioacetals promoted by InCl₃ in refluxing acetonitrile as well as under solvent‐free conditions in excellent yields. This transformation presumably proceeded through the hydroamination–hydroarylation of alkynes, and the Friedländer annulation of active methylene compounds and α‐oxoketene dithioacetals with 2‐aminoarylketones. In addition, simple reductive and oxidative cyclization of 2‐nitrobenzaldehyde and 2‐aminobenzylalcohol, respectively, afforded substituted quinolines. Systematic optimization of the reaction parameters allowed us to identify two‐component coupling (2CC) conditions that were tolerant of a wide range of functional groups, thereby providing densely functionalized/annulated quinolines. This approach tolerates the synthesis of various bioactive quinoline frameworks from the same 2‐aminoarylketones under mild conditions, thus making this strategy highly useful in diversity‐oriented synthesis (DOS). The scope and limitations of the alkyne‐, activated methylene‐, and α‐oxoketene dithioacetal components on the reaction were also investigated.     

An efficient synthesis of fluorine-containing substituted spiro[piperidine-4,4′-pyrano[3,2-c]quinoline]-3′-carbonitrile by nonconventional methods

A series of fluorine-containing substituted spiro[piperidine-4,4′-pyrano[3,2-c]quinolines] were synthesized through a rapid one-pot multi-component reaction under microwave irradiation and sonication. The method has the advantages of excellent yields (80-96%) and short reaction time (3-10 min). We provide a series of fluorinated quinoline derivatives interesting for biological screening tests.     

Synthesis of novel benzo naphtho naphthyridines from 2,4-dicloroquinolines

A schematic study on the condensation of 2,4-dichloroquinolines ( 1 ) with 1-naphthyamine ( 2 ) in the presence of CuI as a catalyst to functionalized mono ( 3 ) and di ( 4 ) substituted naphthylamino quinolines was described. Consequently, these mono- and di-substituted amines on polyphosphoric acid-catalyzed cyclization reaction with p-toluic acid and acetic acid to yield the linear benzo[b]naphtho[2,1-g][1,8]naphthyridines ( 5 ) and angular benzo[b]naphtho[2,1-h] naphthyridines ( 6 ) in good yields. In addition to descried the similar synthesis of benzo[g]naphtho [2,1-b][1,8]naphthyridines ( 12 ) and benzo[h]naphtho[2,1-g][1,8]naphthyridines ( 13 ) from 2,4-dichlorobenzo[h]quinoline ( 8 ) with various anilines ( 9 ) through my intermediates ( 10 and 11 ).     

Synthesis of 5-iodopyrrolo[1,2-a]quinolines and indolo[1,2-a]quinolines via iodine-mediated electrophilic and regioselective 6-endo-dig ring closure

The endo-cyclic ring closure of 1-(2-(substituted ethynyl)phenyl)-1H-pyrroles 3a-t and 1-(2-(substituted ethynyl)phenyl)-H-indole 4a-o mediated by Lewis acid (I(2)) under mild conditions afforded substituted 5-iodopyrrolo[1,2-a]quinolines 5a-t and 5-iodoindolo[1,2-a]quinolines 6a-o in good to excellent yields. The reaction shows selective C-C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-endo-dig-cyclized product. Iodo derivatives of pyrrolo- and indoloquinolines allow functional group diversification on the quinoline nucleus, which proves to be highly advantageous for structural and biological activity assessments.     

Isonitrile trapping reactions under thermolysis of alkoxyamines for the synthesis of quinolines

[reaction: see text] An efficient tandem radical process comprising a thermal alkoxyamine homolysis, an isonitrile trapping reaction, a 5-exo-trig cyclization, and a homolytic aromatic substitution leads to substituted dihydroquinolines. Depending on the substituent R(1), oxidation to dihydro-1H-cyclopenta[b]quinolines (for R(1) = aryl) or tautomerization to tetrahydro-1H-cyclopenta[b]quinolines (for R(1) = CO(2)Me, CN) occurs. The heterocycles are obtained in moderate to good yields. Upon using microwave-induced heating, the reaction time can be shortened from 3 days to 30 min.     

Synthesis of a novel pyrrolo-[3,2-c]quinoline N-oxide by aza-Baylis-Hillman adduct of o-nitrobenzaldehyde

A new and high yielding approach for the synthesis of a novel pyrrolo-[3,2-c]quinoline N-oxide is described. The key step consisted in the palladium-catalyzed reductive cyclization of an uncommon 3-ketopyrrole derivative of o-nitrobenzaldehyde, obtained in a straightforward manner through an aza-Baylis-Hillman/ring closing metathesis/aromatization reaction. A deoxygenation reaction of this novel pyrrolo-[3,2-c]quinoline N-oxide afforded a new substituted pyrrolo-[3,2-c]quinoline analogue.     

New synthetic approach to substituted isoindolo[2,1-a]quinoline carboxylic acids via intramolecular Diels-Alder reaction of 4-(N-furyl-2)-4-arylaminobutenes-1 with maleic anhydride

Acylation of substituted 4-(furyl-2)-4-arylaminobut-1-enes with maleic anhydride provided 2-allyl-6-carboxy-4-oxo-3-aza-10-oxatricyclo[5.2.1.0^1,5]dec-8-enes in high yield under mild reaction conditions. The Diels-Alder adducts are formed via an initial amide formation followed by a stereoselective intramolecular [4+2] exo-cycloaddition reaction. Treatment of the tricyclic compounds with phosphoric acid at high temperatures (70-120 °C) promoted cyclic ether opening, intramolecular cyclization and aromatization to give the corresponding tetracyclic compounds, 5,6,6a,11-tetrahydro-10-carboxyisoindolo[2,1-a]quinolines, in moderate yields. The influence of the acid and the reaction temperature on the cyclization reactions are also discussed.     

Quinaldine derivatives

A new synthesis of substituted 2,5-dimethyl-3,4-dihydro-2H-pyrano[3,2-c]quinolines is realized by heating the corresponding 2-methyl-3-(3-hydroxybutyl)-4-hydroxy(methoxy)-quinoline in polyphosphoric acid. The preparation of ketones of the quinoline series is described.See [1] for communication XXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 534–537, April, 1972.     

Nickel-catalyzed cyclization of 2-iodoanilines with aroylalkynes: an efficient route for quinoline derivatives

An efficient and convenient nickel-catalyzed cyclization of 2-iodoanilines with alkynyl aryl ketones to give 2,4-disubstituted quinolines was developed. The reaction can be employed for the synthesis of naturally occurring quinoline derivatives in good yields. On the basis of the regiochemistry of the products, the possible pathway for the reaction is via the formation of o-aminochalcone.     

Functionalization through lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide. Application to the labeling with carbon-11 of NK-3 receptor antagonist SB 222200

Lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide with the complex n-BuLi/TMEDA (1/1 molar ratio) in THF at -60 degrees C for 5 h occurred selectively at the position 3 of the quinoline ring. This selectivity was shown by the absence of racemization of the stereogenic center and the formation of the corresponding functionalized quinolines in 59-74% yield by subsequent reaction with an electrophile at -60 degrees C for 1 h. The 3-trimethylstannyl derivative was subjected to a Stille reaction using methyl, phenyl, or thienyliodide to afford the alkyl or aryl quinolines in moderate to good yields. This methodology was successfully applied to the radiosynthesis of [11C]SB 222200 using methyl iodide labeled with carbon-11 (beta+ emitter, t1/2=20.4 min) for the in vivo study of NK-3 receptor by positron emission tomography (48-58% radiochemical yields from [11C]CH3I, decay corrected, 45 min total synthesis time).     

Synthesis of new diheteroarylcarbazoles: a facile and simple route of 3,6-di(pyrazol-4-yl)carbazoles

A short and facile route to the synthesis of new 3,6-di(pyrazol-4-yl)carbazoles is reported. Dipyrazolylcarbazoles were synthesized in two steps from 3,6-diacetylcarbazoles through a Vilsmeier reaction which led to the formation of carbazolyl-β-chlorovinyl aldehydes, followed by cyclization with hydrazine hydrate. The reaction of the Vilsmeier reagent with hydrazones of diacetylcarbazoles yielded the corresponding pyrazole dicarbaldehydes in good yields.     

Catalytic synthesis of α-oxoketene S,S-acetals in a wet ionic liquid [Bmim]Cl/H₂O homogeneous system

A clean, practical and environmentally friendly synthesis in a homogeneous system has been developed for α-oxoketene S,S-acetals. A mixture of [Bmim]Cl and water was used as medium. The best economical and practical molar ratio of [Bmim]Cl to substrate was 4 to 1. With various types of 1,3-dicarbonyl compounds as substrate, the corresponding α-oxoketene S,S-acetals have been prepared under mild reaction conditions with yields of 53-74% after purification with silica gel column. [Bmim]Cl/water can be recycled several times.     

Novel and convenient synthesis of substituted quinolines by copper- or palladium-catalyzed cyclodehydration of 1-(2-aminoaryl)-2-yn-1-ols

A general and convenient synthesis of substituted quinolines by regioselective copper- or palladium-catalyzed 6-endo-dig cyclization-dehydration of 1-(2-aminoaryl)-2-yn-1-ols is reported. The crude substrates were easily obtained by the Grignard reaction between the appropriate alkynylmagnesium bromide and 2-aminoaryl ketones and could be used without further purification for the subsequent cyclization step. Heteroannulation reactions were carried out in MeOH or DME as the solvent at 60 or 100 degrees C in the presence of CuCl(2) or PdX(2) (in conjunction with 10 equiv of KX, X = Cl, I) as the catalyst to afford the quinoline derivatives in good to excellent isolated yields based on starting 1-(2-aminoaryl)-2-yn-1-ols (66-90%).