Facile microwave-assisted synthesis of substituted benzofuran derivatives

A series of benzofuran derivatives have been synthesized by use of a microwave-assisted process. Substituted or unsubstituted ο-hydroxyacetophenone and salicylaldehyde reacted with ethyl bromoacetate, ω-bromoacetophenone, or chloroacetone under the action of potassium carbonate in DMF to yield substituted benzofuran derivatives. Compared with conventional heating, this microwave-assisted synthetic process has the advantages of more convenient operation, shorter reaction time, and higher yield.     

Diverse Reactions of Sulfonyl Chlorides and Cyclic Imines

Abstract

Although alkanesulfonyl chlorides react with linear imines to give rise to β-sultam derivatives, in this study, they were reacted with various cyclic imines, including 1-pyrroline, oxazoline, 5,6-dihydro-4H-oxazines and thiazines, 4,5-dihydro-3H-benzo[c]azepine, and 3,4-dihydroisoquinoline, to produce diverse products instead of β-sultam derivatives. The results indicate that alkanesulfonyl chlorides react with cyclic imines to generate N-alkanesulfonyl cyclic iminium ions, which are attacked by nucleophiles, such as water and chloride anion, in the reaction systems, affording addition products. The iminium intermediates cannot undergo a ring closure to form β-sultam derivatives. Arenesulfonyl chlorides showed similar behavior when they reacted with cyclic imines. The scope and limitation of the reaction between sulfonyl chlorides and imines were investigated.

GRAPHICAL ABSTRACT      

The 1,3-Dipolar Cycloadditions of Nitrile Oxides and Nitrile Imines to Alkyl Dicyanoacetates

The readily available alkyl dicyanoacetates 1 reacted with the 1,3-dipolar reagents arenecarbonitrile oxides 2 ′ and arenecarbonitrile imines 5 ′ to afford 1,2,4-oxadiazol and 1,2,4-triazol derivatives. The arenecarbonitrile oxides 2 ′ with electron-donating groups on the arene ring gave products 3a – d resulting from addition on both CN groups of 1 , and those with electron-withdrawing groups provided mono-adducts 4a – e (Scheme 1). Arylnitrile imines 5 ′ reacted with 1 to offer both bis- and mono-addition products (Scheme 2); the bis-adducts 8a , b possess an ester structure, whereas the mono-adducts 6a – d present a ketene-hemiacetal structure.     

Synthesis of 2-Hydrazinylpyridine-3,4-dicarbonitriles and Their Reaction with Salicylaldehyde Derivatives

2-Chloropyridine-3,4-dicarbonitriles reacted with hydrazine hydrate in ethanol to give 2-hydrazinylpyridine- 3,4-dicarbonitriles. Condensation of the latter with salicylaldehyde and its substituted derivatives afforded the corresponding 2-{2-[2-hydroxyphenylmethylidene]hydrazinyl}pyridine-3,4-dicarbonitriles. The fluorescence spectra of the hydrazones obtained from 3-methoxysalicylaldehyde showed sensitivity toward zinc ions.     

Synthesis of nitrogen-containing compounds using chromium Fischer carbene complexes

Synthetic utility of the Fischer-type carbene complexes of chromium for the preparation of nitrogen-containing compounds is demonstrated. Alkoxy carbene complexes reacted with imines to give (optically active) 3-pyrrolines and beta-methoxy allylic amine derivatives in good yields. The amino carbene complexes reacted with alpha,beta-unsaturated aldehydes to give substituted pyrroles in good yields.     

The ruthenium catalyzed formation of chiral dihydropyrrolones from α,β-unsaturated imines: extending the reaction to terminal alkenes and investigating the formation of pyrroles as side-products

The reaction of α,β-unsaturated imines derived from cinnamaldehyde with CO and various alkenes produces chiral 1,3-dihydropyrrolone derivatives. As a byproduct the formation of 2,3-disubstituted pyrroles is observed in every reaction. If the imines are reacted with ethylene only, products with an ethyl group at C-3 of the imine chain are formed. The implications of these findings on the reaction mechanism are discussed.     

Three component coupling reactions of N-acetyl-2-azetine- rapid stereoselective entry to 2,3,4-trisubstituted tetrahydroquinolines

N-Acetyl-2-azetine undergoes Lewis acid catalysed [4 + 2]-cycloaddition with imines derived from aromatic amines and gave a 1:1 mixture of exo-endo diastereoisomeric azetidine cycloadducts which reacted further with aromatic amine, to give 2,3,4-trisubsitituted tetrahydroquinolines in good to excellent yield, predominantly as one diastereoisomer.     

Nickel(0)‐Catalyzed Hydroalkenylation of Imines with Styrene and Its Derivatives

A nickel(0)‐catalyzed hydroalkenylation of imines with styrene and its derivatives is described. A wide range of aromatic and aliphatic imines directly coupled with styrene and its derivatives, thus providing various synthetically useful allylic amines with up to 95 % yield. The reaction offers a new atom‐ and step‐economical approach to allylic amines by using alkenes instead of alkenyl‐metallic reagents. Experiments and DFT calculations showed that TsNH₂ promotes the proton transfer from the coordinated olefin to the imine, accompanied by a new C?C bond formation.     

BF3-promoted cyclization reaction of imines and salicylaldehyde with silyl enol ethers: unexpected formation of dioxaspiro compounds

Unexpected spiro cyclic products were formed from the reaction of imines and salicylaldehyde with silyl enol ethers in the presence of BF₃·OEt₂. Different kinds of dioxaspiro products were afforded depending on the nature of starting materials. Furthermore, salicylaldehyde could also react directly with several silyl enol ethers, giving three products with different spiro cyclic structure under the same reaction conditions.     

Parallel approach for solution-phase synthesis of 2-quinoxalinol analogues and their inhibition of LPS-induced TNF-alpha release on mouse macrophages in vitro

A parallel solution-phase synthesis of 2-quinoxalinol analogues is described. The key step-simultaneous reductions of m-Ar(NO(2))(2) to m-Ar(NH(2))(2) was investigated extensively. We obtained preliminary pharmacological activity of those analogues for the inhibition of LPS-induced TNF-alpha release on mouse macrophage in vitro. Two compounds revealed inhibitory activity, with IC(50) values of 0.40 microM (7-amino-6-[(3-methoxypropyl)amino]-3-methyl-2-quinoxalinol) and 2.2 microM (7-amino-6-[(3-butoxypropyl)amino]-3-methyl-2-quinoxalinol), respectively.     

Diastereoselective reduction of ketimines derived from (R)-3,4-dihydroxybutan-2-one: an alternative route to key intermediates for the synthesis of anticancer agent ES-285

A simple and convenient procedure for the diastereoselective reduction of imines derived from (R)-3,4-dihydroxybutan-2-one is described. The use of sodium borohydride as a reducing agent in the reactions with pre-synthesised imines gave aminodiol derivatives with the appropriate stereochemistry for use as intermediates in the synthesis of anticancer agent ES-285. The aminodiols were isolated in ca. 62% yield.     

Task-Specific Ionic Liquid as Reagent and Reaction Medium for the One-Pot Horner–Wadsworth–Emmons–Type Reaction Under Microwave Irradiation

A task-specific imidazolium-based phosphinite ionic liquid (IL-OPPh₂) was used as the dual solvent–reagent for the synthesis of E-cinamates and coumarin derivatives via the one-pot Horner–Wadsworth–Emmons–type reaction. The ionic liquid containing its corresponding phosphinite moiety was reacted with α-chloro esters and benzaldehyde or salicylaldehyde derivatives in the presence of sodium methoxide under microwave irradiation to produce the related E-cinamates or coumarins, respectively. The satisfactory results were obtained with good yields, short reaction time, and simple experimental procedure.     

Synthesis of a novel series of 3-substituted [1]benzothieno[3,2-d]pyrimidine derivatives

A series of 3-substituted [1]benzothieno[3,2-d]pyrimidine derivatives has been synthesized as possible antileukemic agents by condensation of methyl 3-(ethoxymethylene)amino-2-benzothiophene carboxylate (II) with a variety of amines to afford the corresponding 3-aryl and 3-alkyl [I]benzothieno[3,2-d]pyrimidin-4(3H)-ones, Ill and IV, respectively. In addition, Mannich reactions of [I]benzothieno[3,2-d]pyrimidin-4(3H)-one (VIII) with formaldehyde and secondary amines gave the expected derivatives, IX. 3-Amino[I]benzothieno[3,2-d]-pyrimidin-4(3H)-one (VI) reacted with substituted aromatic aldehydes in the presence of boron trifluoride to yield the corresponding imines VII.     

Generation and metathesis of azomethine imines in reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with het(aryl)methylidenemalononitriles

A new metathesis reaction of azomethine imines is found. Catalytic or thermal diaziridine ring opening of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes leads to azomethine imines reacting further with het(aryl)methylidenemalononitriles to give in situ new azomethine imines inaccessible by common synthetic methods. New azomethine imines are detected as pyrazolines formed via a 1,4-H shift and trapped by the [3+2] cycloaddition with various dipolarophiles to yield 1,5-diazabicyclo[3.3.0]octane derivatives bearing pharmacophoric heterocycles, e.g. furan, nitrofuran, thiophene, and indole. The best results are achieved in the Et₂O·BF₃-catalyzed reactions in ionic liquids.     

Azomethine derivatives of aluminium containing AlOSiMe3 groups

The synthesis of azomethine derivatives of aluminium containing AlOSiMe₃ groups and resistant to hydrolysis is described. These have been prepared either by the equimolar reactions of bibasic tridentate or bibasic tetradentate azomethines, viz. N-(2- mercaptoethyl) salicylaldimine, N-(2-mercaptophenyl) salicylaldimine, salicylaldehyde sulphisoxazole, salicylaldehyde azine, salicylaldehyde semicarbazone, salicylaldehyde thiosemicarbazone, o-hydroxyacetophenone azine N,N' 1,3-propylene-bis(salicylaldimine) and diacetyl bis(2-mercaptoanil), or of 1 : 2 molar reactions of monobasic bidentate imines viz. N-(2-mercaptophenyl) benzaldimine, benzaldehyde semicarbazone and benzaldehyde thiosemicarbazone with Me₃SiOAl(OPrⁱ)₂ in the medium of dry benzene. The resulting derivatives are coloured solids with sharp m.ps, non-volatile, non-electrolytes, soluble in chloroform, dimethylformamide and dimethylsulphoxide, and monomeric in nature. Their IR,¹H NMR and electronic spectral data have been presented in support of the proposed structures.     

1,2‐Bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile and Vinyl Ethers: Cyclic Ketene Imines on the Pathway to 1 : 2 Cycloadducts

(E)‐ and (Z)‐1,2‐bis(trifluoromethyl)ethene‐1,2‐dicarbonitrile (BTE; (=E)‐ and (Z)‐1,2‐bis(trifluoromethyl)but‐2‐enedinitrile) were reacted with an excess of methyl vinyl ether, used as solvent, and furnished 1 : 2 adducts 6 (54%) and cyclobutanes 3 as 1 : 1 adducts (41%). The four diastereoisomeric bis‐adducts 6 (different ratios from (E)‐ and (Z)‐BTE) are derivatives of 1‐azabicyclo[4.2.0]oct‐5‐ene; X‐ray analyses and ¹⁹F‐NMR spectra revealed their structures. Since the cyclobutanes 3 are resistant to vinyl ether, the pathways leading to mono‐ and bis‐adducts must compete on the level of the intermediate l,4‐zwitterions 1 and 2 . The latter either cyclize to the cyclobutanes 3 or to six‐membered cyclic ketene imines 8 which accept a second molecule of vinyl ether to yield the bis‐adducts 6 . The occurrence of the highly strained ketene imines 8 gains credibility by comparison to stable seven‐membered cyclic ketene imines recently reported.     

Reactions with the Arylhydrazones of α-Cyanoketones: The Structure of 2-Arylhydrazono-3-ketimino-nitriles

Analysis of the IR., UV., and polarographic data of a variety of 2-arylhydrazono-3-ketimino-nitriles indicated that these derivatives exist mainly in the intramolecularly chelated hydrazone structure 1 . Compounds 1 reacted with hydrazine hydrate to yield the corresponding 5-amino-4-arylazopyrazoles ( 3 ). Compounds 3a reacted with acetylacetone, ethyl acetoacetate, and diethyl malonate to yield the pyrazolo[1, 5-a]pyrimidine derivatives 4, 5 , and 7 respectively. Compound 3a also reacted with benzoylisothiocyanate to yield the pyrazolyl thiourea derivative 8 .     

Preparation and reactions of polymeric azides. III. The preparation and reactions of polymeric phosphine imines

Polymeric azides reacted with triphenylphosphine to give the corresponding phosphine imines, which reacted with bases, aldehydes, and isocyanates to give amines, imines, and carbodiimides, respectively.     

Stereocontrolled aziridination of imines via a sulfonium ylide route and a mechanistic study

The reaction of N-diphenylphosphinoyl imines 1 with [3-(trimethylsilyl)allyl]dimethylsulfonium bromide (5) in the presence of NaH at room temperature predominantly gave trans-vinylaziridines 4. On the other hand, cis-vinylaziridines 4 were the main products when the preformed ylide prepared from the reaction of [3-(trimethylsilyl)allyl]diphenylsulfonium perchlorate (6) was reacted with the same imines 1 at low temperature. trans-Aziridines were also obtained when imines 1 and sulfinimines 9 were reacted with N,N-dimethylacetamide-2-dimethylsulfonium bromide (7) in the presence of a base, respectively. A mechanistic study showed that the stereochemistry of these reactions was controlled by the reactivity of the imines and ylides. A higher reactivity of imines and ylides favors the formation of cis-aziridines, whereas a lower reactivity leads to trans-products.     

Synthesis of 2-substituted 2H-chromenes using potassium vinyltrifluoroborates

2H-Chromenes were synthesized from salicylaldehyde using potassium vinylic borates in the presence of secondary amines. We synthesized these 2H-chromene derivatives as a part of an ongoing project to develop inhibitors for TGF-β receptors. Potassium vinyl trifluoroborates react with salicylaldehydes at 80 °C in the presence of a secondary amine and produced 2-substituted 2H-chromene derivatives with a 70-90% yield.