Efficient One-Pot Synthesis of 2,2-Dimethyl-2H-chromenes via Pd(II)-Catalyzed Coupling and SiO2-Promoted Condensation of o-Halophenols with 2-Methyl-3-buten-2-ol

An efficient synthesis of 2,2-dimethyl-2H-chromenes was accomplished by Pd(II)-catalyzed coupling and SiO₂-promoted condensation of o-halophenols with 2-methyl-3-buten-2-ol (1,1-dimethylallyl alcohol) in one pot. The method is very general and can be useful for the synthesis of some natural 2,2-dimethyl-2H-chromenes.     

Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac₂O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties.     

Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.     

ZnCl2 Promoted Formal (3+2) Cycloaddition Reactions of 2-Alkoxy-1,4-benzoquinones with 2H-Chromenes

A simple, mild, inexpensive and highly efficient method for the synthesis of 2,2-dimethyldihydropyranopterocarpans (4a–h and 5a–b) by formal (3+2) cycloaddition reactions of 2-alkoxy-1,4-benzoquinones (3a–b) with 2H-chromenes (1a–d and 2) using ZnCl₂ at room temperature has been developed.     

An expeditious and greener one-pot synthesis of 4H-chromenes catalyzed by Ba(OTf)2 in PEG-water

Abstract

An expeditious synthesis of 4H-chromenes has been achieved by three-component one-pot condensation of 1,3-diketone, aldehyde, and malononitrile using Ba(OTf)₂ as catalyst in PEG-water at room temperature. Results from various reaction media and different metal triflates as catalysts show that choice of proper catalyst and the solvent system play a key role in the synthesis of 4H-chromene-3-carbonitrile derivatives. The catalyst can be recovered and reused at least five times without loss of activity. The application of an eco-friendly, noncorrosive, and reusable catalytic system with high isolated yield of the products makes this method advantageous.     

ReCl(CO)5-catalyzed cyclocondensation of phenols with 2-methyl-3-butyn-2-ol to afford 2,2-dimethyl-2H-chromenes

A direct one-pot route for the synthesis of 2,2-dimethyl-2H-chromenes by Re(CO)₅Cl-catalyzed cyclocondensation of phenols with 2-methyl-3-butyn-2-ol has been developed. The easy availability of starting materials, mild reaction conditions, high atom-efficiency, and the use of a recoverable catalyst are advantages of this procedure.     

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.     

Fluorinated chromenes. III. Synthesis of 3-fluoro-2,2-dimethyl-2H-chromenes

The reaction of 2-fluoro-1,1-dimethoxy-3-methylbut-2-ene ( 3 ) with phenols in dry pyridine leads to 3-fluoro-2,2-dimethyl-2H-chromenes. 3-Fluoro analogues of the natural insect antijuvenile hormones Precocene I ( 1a ) and II ( 1b ) have been prepared by this method.     

Synthesis of 2-amino-3-cyano-4H-chromen-4-ylphosphonates and 2-amino-4H-chromenes catalyzed by tetramethylguanidine

Synthesis of 2-amino-4H-chromen-4-ylphosphonates and 2-amino-4H-chromenes has been accomplished by the reaction of salicylaldehyde, malononitrile, dialkyl/diphenylphosphites catalyzed by 1,1,3,3-tetramethylguanidine (TMG) under neat conditions at room temperature. The applicability of catalytic TMG for the synthesis of 2-amino-4H-chromenes also has been described. The mild reaction conditions, simple work-up procedure, and use of TMG as an inexpensive catalyst provides an economical protocol for the preparation of important phosphorus-containing compounds.     

Reactions of 3-nitro-2-trihalomethyl-2H-chromenes with C-nucleophiles. Synthesis of 3-nitro-4-(pyrazol-4-yl)-2-trihalomethylchromanes

The nucleophilic addition of acetylacetone and ethyl acetoacetate at the double bond of 3-nitro-2-trihalomethyl-2H-chromenes in the presence of NaH affords 2,3,4-trisubstituted chromanes containing the β-dicarbonyl fragment at position 4. The trans-trans configuration and the enol structure of the reaction products were confirmed by ¹H NMR spectroscopy and X-ray diffraction. Treatment of these compounds with hydrazine gives the corresponding 3-nitro-4-(pyrazol-4-yl)-2-trihalomethylchromanes. The reactions of 3-nitro-2-trihalomethyl-2H-chromenes with nitromethane and nitroethane in the presence of K₂CO₃ produce 1,3-dinitro derivatives of the chromane series. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1945–1955, November, 2006.     

Synthesis of benzopyran derivatives,XV Preparation of arylsulfonyloxy-2,2-dimethyl-2H-chromenes

Summary Arylsulfonyloxy-2,2-dimethyl-2H-chromenes (26–35) have been synthesized by reduction of arylsulfonyloxy-2,2-dimethyl-4-chromanones (6–15) followed by dehydration.

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Synthese von Benzopyranderviaten. 15. Mitt.: Darstellung von Arylsulfonyloxy-2,2-dimethyl-2H-chromenen

Zusammenfassung Reduktion von Arylsulfonyloxy-2,2-dimethyl-4-chromanonen (6–15) und anschließende Dehydratisierung liefert Arylsulfonyloxy-2,2-dimethyl-2H-chromene (26–35).

     

Reaction between alkyl isocyanides and dimethyl acetylenedicarboxylate in the presence of polyhydroxybenzenes. Synthesis of 4H-chromene derivatives

The reactive intermediate generated by the addition of alkyl isocyanides to dimethyl acetylenedicarboxylate was trapped by phenols such as resorcinol, catechol, hydroquinone, pyrogallol, 2,4-dihydroxybenzaldehyde, or 8-hydroxyquinoline to produce highly functionalized 4H-chromenes in fairly good yields.     

γ-Lactonizations of 2H-chromenes via cyclopropanation

A two-step synthesis of tetrahydro-2H-furochromenones from 2H-chromenes is reported. The reaction of a series of tert-butyl 2-diazoacetate derivatives with 2H-chromenes, catalyzed by Rh₂(OAc)₄, generated cyclopropane intermediates that rearranged to γ-lactones on treatment with Sn(OTf)₂.     

Cu@KCC-1-NH-CS2 as a new and highly efficient nanocatalyst for the synthesis of 2-amino-4H-chromene derivatives

In the present work, Cu@KCC-1-NH-CS₂ as a green, efficient, and reusable nano-reactor was designed and used for the one-pot, three-component synthesis of 2-amino-4H-chromene derivatives using the reaction of cyclic 1,3-diketones, arylglyoxals, and malononitrile, under reflux conditions in EtOH. Engineered nanocatalyst characterized using different methods including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), adsorption/desorption analysis (BET), and energy dispersive X-ray spectroscopy (EDS). According to the obtained results, presented protocol for the synthesis of 2-amino-4H-chromenes using Cu@KCC-1-NH-CS₂ gave the desired products in higher yields (89–98%) with short reaction times. Also, under mild reaction conditions this green nanocatalyst indicated recyclable behavior five times with minor reduce in its catalytic activity.     

Facile construction of 4H-chromenes via Michael addition of phenols to benzylidene oxobutanoates and their successful conversion into pyranocoumarins

An efficient and simple approach for the synthesis of functionalized 4H-chromenes has been developed via acid catalyzed Michael addition of phenols to benzylidene oxobutanoates. Preliminary mechanistic studies were conducted, suggesting that intermediate chroman derivative is initially formed which on dehydration produces final 4H-chromene. The conversion of 4H-chromenes into linear and angular pyranocoumarins is also described. The structural arrangements between the pyran and coumarin rings have been established by X-ray crystallographic analysis and 2D NMR spectroscopy.     

First example of regioselective nucleophilic 1,6-addition of trimethyl(trifluoromethyl)silane to 4H-chromene derivatives

Condensation of 2-trifluoromethylchromone with diethyl malonate, ethyl cyanoacetate, and Meldrum’s acid gave the corresponding methylidene derivatives of 2-trifluoromethyl-4H-chromene. Nucleophilic 1,6-addition of an excess of Me₃SiCF₃ in the presence of Me₄NF to those obtained from the former two compounds afforded 4-substituted 2,2-bis(trifluoromethyl)-2H-chromenes. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1628–1630, September, 2006.     

PEG-400 remarkably efficient and recyclable media for one-pot synthesis of various 2-amino-4H-chromenes

Abstract

Polyethylene glycol-400 has been found to be a recyclable and rapid reaction medium for the synthesis of 2-amino-4H-chromenes by the condensation of aromatic aldehyde, malononitrile, and α-naphthol. This method gives remarkable advantages such as simple work up, high yields, and a greener method by avoiding toxic catalyst and hazardous solvents.     

Über die Umsetzung von 2-Methyl-2,5-diphenyl-imidazolin-4-thion und 2-Methyl-2,5-diphenyl-4-chlor-2H-imidazol mit aliphatischen und aromatischen Aminen,Alkoholen und Phenolen

Zusammenfassung Aliphatische Amine bzw. Alkohole reagiren (in Gegenwart von PbO) mit 2-Methyl-2,5-diphenyl-imidazolin-4-thion (1) glatt zu 4-Alkylamino-2H-imidazolen (2 a-f, 7) bzw. 4-Alkoxy-2H-imidazolen (9 a-g). Die Darstellung von 4-Arylamino-2H-imidazolen (4 a-j) bzw. 4-Aroxy-2H-imidazolen (10 a-t) gelingt in guten Ausbeuten durch Umsetzung von 2-Methyl-2,5-diphenyl-4-chlor-2H-imidazol (3) mit aromatischen Aminen in siedenden Lösungsmitteln (Petroläther, Aceton) bzw. mit Phenolen in siedendem Aceton in Gegenwart von HCl-Acceptoren (K₂CO₃, Dabco). Die Umsetzung von3 mit Anthranilsäure liefert in 83proz. Ausbeute 1-Methyl-1,3-diphenyl-1H, 9H-imidazo[5,1-b]chinazolin-9-on (6). Aus3 und Thiophenol erhält man glatt 2-Methyl-2,5-diphenyl-4-phenylthio-2H-imidazol (11).

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On the reaction of 2-Methyl-2,5-diphenyl-imidazoline-4-thione and 2-Methyl-2,5-diphenyl-4-chloro-2H-imidazole with aliphatic and aromatic amines, alcohols and phenols (joint action of elemental sulfur and gaseous ammonia upon ketones, LXXVI

Aliphatic amines and alcohols (in the presence of PbO) easily react with 2-methyl-2.5-diphenyl-imidazoline-4-thione (1) to 4-alkylamino-2H-imidazoles (2 a-f, 7) and 4-alkoxy-2H-imidazoles (9 a-g), resp. 4-arylamino-2H-imidazoles (4 a-j) are prepared in good yields by the reaction of 2-methyl-2.5-diphenyl-4-chloro-2H-imidazole (3) with aromatic amines under reflux in light naphtha or acetone; in the same manner 4-aroxy-2H-imidazoles (10 a-t) are obtained from3 and phenols in boiling acetone in the presence of HCl-acceptors (K₂CO₃, Dabco). Reaction of3 with anthranilic acid leads to1-methyl-1.3-diphenyl-1H.9H-imidazo[5.1-b]chinazoline-9-one (6) in 83% yield. By reaction of thiophenol with3 2-methyl-2.5-diphenyl-4-phenylthio-2H-imidazole (11) is easily obtained.

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Herrn Prof. Dipl.-Ing., Dr. techn., Dr. e. h.Otto Kratky zum 70. Geburtstag herzlichst gewidmet.

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Teil der DiplomarbeitJ. Gräber, Techn. Hochschule Aachen, 1970.

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Teil der DiplomarbeitU. Lames, Techn. Hochschule Aachen, 1971.     

The scope of the Heck arylation of enol ethers with arenediazonium salts: a new approach to the synthesis of flavonoids

The scope of the Heck arylation of cyclic and acyclic enol ethers with arenediazonium salts was evaluated. Arylation of 2,3-dihydrofuran yielded 2-aryl-2,5-dihydrofurans as the major adducts (>99:1) except when using n-Bu₄NHSO₄ as additive or 4-NO₂PhN₂BF₄ as arenediazonium salt. 2,3-Dihydropyran provided mixtures of the three possible isomeric Heck adducts. Arylation of n-butylvinylether with arenediazonium bearing electron-donating groups resulted in substituted acetophenones as almost exclusive products in good overall yields. Substituted 4H-chromenes provided 2-aryl-2H-chromenes in moderate yield when applying the Pd(OAc)₂/2,6-di-t-butyl-4-methylpyridine catalytic system, which were applied in the synthesis of flavonoids.     

Synthesis of 2,2-Disubstituted 2H-Chromenes through Carbon-Carbon Bond Formation Utilizing a [1,2]-Phospha-Brook Rearrangement under Brønsted Base Catalysis

A new methodology for the synthesis of 2,2-disubstituted 2H-chromenes was developed by utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. Phosphazene P2-tBu efficiently catalyzed the addition reaction of 4H-chromen-4-ols containing a diethoxyphosphoryl group with α,β-unsaturated ketones, which involved the catalytic generation of a carbanion through the [1,2]-phospha-Brook rearrangement and subsequent conjugate addition at the 2-position to afford adducts possessing an alkenylphosphate moiety in a highly diastereoselective manner. Further transformation of the adducts based on a nickel-catalyzed cross-coupling reaction with arylzinc reagents provided densely functionalized 2,2-disubstituted 2H-chromenes.