Pictet‐Spengler Condensation of N,N‐Dimethylsulfamoyl‐β‐Phenethylamines with Methylthioacetic Acid Ethyl Ester. New Synthesis of Ethyl 1,2,3,4‐Tetrahydroisoquinoline‐1‐Carboxylates

The reaction of N,N‐dimethylsulfamoyl‐β‐phenethylamines with methylthioacetic acid ethyl ester using phenyliodine(III) bis(trifluoroacetate) gives moderate to good yields of the corresponding ethyl 1,2,3,4‐tetrahydroisoquinoline‐1‐carboxylates.     

New trans/cis tetrahydroisoquinolines. 1. trans‐2‐benzyl‐3‐(l‐methyl‐1h‐pyrrol‐2‐yl)‐4‐substituted‐1,2,3,4‐tetrahydroisoquinolin‐1‐ones and corresponding tetrahydroisoquinolines

The reaction of homophthalic anhydride and N‐(1‐methyl‐1H‐pyrrol‐2‐yl‐methylidene)‐benzylamine in boiling benzene afforded as a main product the expected substituted trans‐1,2,3,4‐tetrahydroisoquinoline‐4‐carboxylic acid 5 . The carboxylic group of 5 was transformed in four steps into cyclic amino‐methyl groups yielding numerous new tetrahydroisoquinolinones 11a‐j incorporating a given fragment of pharmacological interest. Reduction of 11a‐j was studied.     

Synthesis of trans/cis‐3,4‐Disubstituted 1,2,3,4‐Tetrahydroisoquinolines by Nucleophilic Acyl Substitution of Homophthalic Anhydride with Aldimines

The reaction of the functionalized N‐protected imines 3 and 7 containing either the chloromethyl or ethyl ester moieties, respectively, attached to the imine carbon with homophthalic anhydride 2 afforded cis/tran‐3‐subsituted‐1‐oxo‐1,2,3,4‐tetrahydroisoquinoline‐4‐caboxylic acids appropriate for further synthetic elaboration.     

Silyl modification of biologically active compounds. 13. Synthesis,cytotoxicity and antibacterial action of N‐methyl‐N‐(2‐triorganylsiloxyethyl)‐1,2,3,4‐tetrahydro(iso)quinolinium iodides

A series of N‐methyl‐N‐(2‐triorganylsiloxyethyl)‐1,2,3,4‐tetrahydro(iso)quinolinium iodides has been synthesized via dehydrocondensation reaction of N‐(2‐hydroxyethyl)‐1,2,3,4‐tetrahydroisoquinoline, N‐(2‐hydroxyethyl)‐1,2,3,4‐tetrahydroquinoline and 4,4‐dimethyl‐N‐(2‐hydroxyethyl)‐4‐sila‐1,2,3,4‐tetrahydroisoquinoline with trialkyl(aryl)hydrosilanes and subsequent alkylation, and characterized by ¹H, ¹³C and ²⁹Si NMR and mass spectroscopy. The biological activity data exhibited a marked enhancement of inhibitory activity against tumour cell lines and almost all the test bacterial/fungal strains in comparison with their 2‐hydroxyethyl precursors. Cytotoxicity in the microgram range against HT‐1080 (human fibrosarcoma) and MG‐22A (mouse hepatoma) cancer cell lines was observed for most of compounds. Copyright © 2012 John Wiley & Sons, Ltd.     

An Approach to the Synthesis of Spiro[indene‐pyridoisoquinoline] Derivatives via 1,4‐Dipolar Cycloaddition of Isoquinoline and Acetylene Esters,and (1,3‐Dihydro‐1,3‐dioxo‐2H‐inden‐2‐ylidene)malononitrile

A concise and efficient approach to the spiro‐tetrahydroisoquinoline derivatives has been developed by 1,4‐dipolar cycloaddition of zwitterions resulting from isoquinoline and acetylene esters and (1,3‐dihydro‐1,3‐dioxo‐2H‐inden‐2‐ylidene)malononitrile in MeCN at room temperature. The significance of this method lies in good yields and ease of product purification, and no inert atmosphere is required. The structures of the products were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme).     

Copper‐Catalyzed Aerobic Oxidative Ring Expansion of Isatins: A Facile Entry to Isoquinolino‐Fused Quinazolinones

A copper‐catalyzed aerobic oxidative ring expansion reaction of isatins with 1,2,3,4‐tetrahydroisoquinoline for the synthesis of tetracyclic quinazolinones has been developed. This reaction is performed smoothly under simple conditions to give the corresponding products in moderate to good yields with good functional group tolerance. The capacity of the resultant 5H‐isoquinolino[1,2‐b]quinazolin‐8(6H)‐one for a range of palladium‐catalyzed directing C—H activation has been further demonstrated, thus giving a broader access to diverse tetracyclic quinazolinones.     

The preparation of covalent triazine‐based framework via Friedel‐Crafts reaction of 2,4,6‐trichloro‐1,3,5‐triazine with N,N′‐diphenyl‐N,N′‐di(m‐tolyl)benzidine for capturing and sensing to iodine

The covalent triazine‐based framework (TDPDB) has been prepared by Friedel‐Crafts polymerization reaction of N,N′‐diphenyl‐N,N′‐di(m‐tolyl)benzidine (DPDB) with 2,4,6‐trichloro‐1,3,5‐triazine (TCT) catalyzed by methanesulfonic acid. The yield of the reaction (94.85%) is very high. TDPDB was provided with Brunauer‐Emmett‐Teller specific surface area of 592.18 m² g^?1 and pore volume of 0.5241 cm³ g^?1. TDPDB demonstrated an excellent capacity for capturing iodine (3.93 g g^?1) and an outstanding ability to fluorescent sensing to iodine with Ksv of 5.83 × 10⁴ L mol^?1. It also showed high fluorescent sensing sensitivity to picric acid.     

Synthesis of 1‐methyl‐, 4‐nitro‐, 4‐amino‐and 4‐iodo‐1,2‐dihydro‐3H‐pyrazol‐3‐ones

4‐Aminopyrazole‐3‐ones 4b, e, f were prepared from pyrazole‐3‐ones 1b‐d in a four‐step reaction sequence. Reaction of the latter with methyl p‐toluenesulfonate gave 1‐methylpyrazol‐3‐ones 2b‐d . Compounds 2b‐d were treated with aqueous nitric acid to give 4‐nitropyrazol‐3‐ones 3b‐d. Reduction of compounds 3b‐d by catalytic hydrogenation with Pd‐C afforded the 4‐amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole‐3‐ones derivatives 2c, d were reduced into aminopyrazole‐3‐ones 5e, f. 4‐Iodopyrazole‐3‐ones 7a, 7c and 8 were prepared from the corresponding pyrazol‐3‐ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride.     

Convergent Synthesis of (−)‐Quinocarcin Based on the Combination of Sonogashira Coupling and Gold(I)‐Catalyzed 6‐endo‐dig Hydroamination

The total synthesis of the pentacyclic tetrahydroisoquinoline alkaloid quinocarcin, which possesses intriguing structural and biological features, has been achieved through a gold(I)‐catalyzed regioselective hydroamination reaction. It is noteworthy that the regioselectivity of the intramolecular hydroamination of an unsymmetrical alkyne could be completely switched through substrate control. Other key features of this synthesis include the highly stereoselective synthesis of 2,5‐cis‐pyrrolidine through the intramolecular amination of the bromoallene and the Lewis acid mediated ring opening of dihydrobenzofuran.     

Molecular Iodine Catalyzed One‐pot Aza‐Diels‐Alder Reaction under Solvent‐free Conditions

Catalyzed by molecular iodine at room temperature, under solvent‐free conditions, a two component aza‐Diels‐Alder cyclization of N‐vinyl‐2‐pyrrolidinone with N‐arylimine gave tetrahydroquinoline derivatives in good yields and high stereo‐selectivity. And three components aza‐Diels‐Alder reaction of N‐vinyl‐2‐pyrrolidinone, anilines and indole‐3‐carbaldehydes under the same condition afford only cis‐product in good yields.     

An Efficient Method for the Synthesis of 3‐Aryl‐4,7‐phenanthroline Derivatives Catalyzed by Iodine

A mild and efficient method for the synthesis of 3‐aryl‐4,7‐phenanthroline derivatives via three‐component reaction of aromatic aldehyde, quinolin‐6‐amine, and n‐butylvinyl ether is described using iodine as catalyst. The features of this procedure are mild reaction conditions, good to high yields, and operational simplicity.     

Unusual Chemoselective RhII‐Catalysed Transformations of α‐Diazocarbonyl Piperidine Cores

The reactivity of various α‐diazocarbonyl piperidine scaffolds, characterised by an increased molecular complexity, was tested with various Rh^II catalysts. The structure of the starting reagent is of relevance to the synthetic results. An unexpected dimerisation took place, starting from the simple piperidine scaffold, to give the hexahydrotetrazine ring system. Products derived from a nitrogen ylide intermediate or aromatic substitution (1,3,4,5‐tetrahydro‐2,5‐methanobenzo[c]azepine and 1,2,3,3a‐tetrahydrocyclopenta[de]isoquinolin‐4(5 H)‐one rings, respectively) were obtained from tetrahydroisoquinoline derivatives. The chemoselectivity of the reaction could be controlled by the choice of starting reagent, Rh^II catalyst and the reaction conditions. Finally, it was found that the azepino heterocycle could coordinate to the catalyst to give new Rh^II complexes.     

Hypervalent‐Iodine‐Mediated Carbon–Carbon Bond Cleavage and Dearomatization of 9H‐Fluoren‐9‐ols

A transition‐metal‐free synthesis of spiro compounds from 9H‐fluoren‐9‐ols mediated by hypervalent iodine is reported. In this reaction, an unprecedented β‐carbon elimination of tertiary alkoxyliodine(III) to form new diaryliodonium salts is proposed. The obtained phenol intermediates undergo oxidative dearomatization to furnish a class of oxo‐spiro compounds. This domino reaction significantly increases the complexity of these molecules and shows excellent regio‐ and stereoselectivity.     

Synthesis of 1‐(3,4‐dimethoxyphenylmethyl)‐3‐phenyl‐6,7,8‐trimethoxy‐3,4‐dihydroisoquinoline

In an attempt to ascertain the scope of using ethyl polyphosphate in the Bischler‐Napieralsky annelation reaction, a title compound was synthesized and reduced to the respective 1‐(3,4‐dimethoxyphenylmethyl)‐3‐phenyl‐6,7,8‐trimethoxy‐1,2,3,4‐tetrahydroisoquinoline.     

A Selective Method for the Synthesis of N,N’‐diarylbenzene‐1,4‐diamine and Dispirocyclic Quinazolinone Derivatives Catalyzed by Iodine

The same iodine‐catalyzed reaction of 2‐aminobenzamides with cyclohexane‐1,4‐dione in THF, selectively gives N,N’‐diarylbenzene‐1,4‐diamine and dispirocyclic quinazolinone derivatives. The former or latter depends on the 2‐aminobenzamides.     

Synthesis of Substituted α‐(Hydroxymethyl)‐β‐iodoacrylates via MgI2‐Promoted Stereoselective Aldol Coupling

The efficient and highly stereoselective syntheses of a variety of (Z)‐configured, substituted α‐(hydroxymethyl) ‐ β‐iodo‐acrylates from prop‐2‐ynoate and various aldehydes was achieved. The synthetic protocol involves a simple one‐pot coupling reaction under mild conditions, promoted by MgI₂, which serves both as a Lewis acid and iodine source for a Baylis? Hillman‐type reaction. All adducts were generated in good‐to‐excellent yields, the (Z)‐isomers being formed in high selectivity (>98%). The conversion of methyl prop‐2‐ynoate into an active ‘β‐iodo allenolate’ intermediate, which then nucleophilically attacks an aldehyde, is proposed as a plausible reaction mechanism.     

A Green Synthesis of Pyrido[1,2‐a]quinazoline‐1,6‐dione Derivatives in Ionic Liquid Catalyzed by Iodine

A mild, green, and facile route to the synthesis of 3,4,4a,5‐tetrahydro‐4a‐methyl‐2H‐pyrido[1,2‐a]quinazoline‐1,6‐dione derivatives has been developed. In the presence of iodine, a variety of 2‐aminobenzamides underwent a tandem reaction with 6‐chlorohexan‐2‐one to afford the corresponding pyridoquinazolines in good to high yields.     

A Green Synthesis of Pyrrolo[1,2‐a]quinazolin‐5(1H)‐one Derivatives in Ionic Liquids Catalyzed by Iodine

A series of 2,3,3a,4‐tetrahydro‐3a‐methylpyrrolo[1,2‐a]quinazolin‐5(1H)‐one derivatives were synthesized by a reaction of 2‐aminobenzamide and 5‐chloropentan‐2‐one at 80 °C catalyzed by iodine in ionic liquid of [BMIm]Br. Compared with the other methods, this novel method has the advantages of milder reaction conditions, high yields, environmental benignity, and metal‐free catalyst.     

Intramolecular Metal‐Free Oxidative Aryl–Aryl Coupling: An Unusual Hypervalent‐Iodine‐Mediated Rearrangement of 2‐Substituted N‐Phenylbenzamides

Hypervalent‐iodine‐mediated oxidative coupling of the two aryl groups in either 2‐acylamino‐N‐phenyl‐benzamides or 2‐hydroxy‐N‐phenylbenzamides, with concomitant insertion of the ortho‐substituted N or O atom into the tether, has been described for the first time. This unusual metal‐free rearrangement reaction involves an oxidative C(sp²)? C(sp²) aryl–aryl bond formation, cleavage of a C(sp²)? C(O) bond, and a lactamization/lactonization. Furthermore, unsymmetrical diaryl compounds can be easily obtained by removing the tether within the cyclized product.     

The Chemo‐selective Reaction of 2‐Amino‐N′‐arylbenzohydrazide and Ketonic Acid Catalyzed by Iodine for the Synthesis of Quinazoline Derivatives

The chemo‐selective reaction of 2‐amino‐N′‐arylbenzohydrazide and ketonic acid catalyzed by iodine was used to synthesize various 2,3‐dihydroquinazolin‐4(1H)‐ones efficiently. The use of levulinic acid furnished a series of 2,3,3a,4‐tetrahydropyrrolo[1,2‐a]quinazoline‐1,5‐diones in high yields, while acetobutyric acid only afforded the quinazoline skeletons without forming the second pyridine ring. Using alcohol as the solvent instead of ionic liquids, a subsequent esterification was performed with the carboxylic group of acetobutyric acid substrate in one‐pot manner.