An Efficient Synthesis of Benzo[g]thiazolo[2,3‐b]quinazolin‐4‐ium and Benzo[g]benzo[4,5]thiazolo[2,3‐b]quinazolin‐14‐ium Hydroxides by a One‐pot,Three‐component Reaction under Green Conditions

A new series of benzo[g]thiazolo[2,3‐b]quinazolin‐4‐ium and benzo[g]benzo[4,5]thiazolo[2,3‐b]quinazolin‐14‐ium hydroxide derivatives have been synthesized by the one‐pot, three‐component reaction of aryl glyoxal monohydrates, 2‐hydroxy‐1,4‐naphthoquinone, and 2‐aminothiazole or 2‐aminobenzothiazole in the presence of triethylamine and p‐toluenesulfonic acid as organocatalysts in H₂O/acetone (2:1) at room temperature. This method offers mild reaction conditions, excellent yields, easy workup, and readily accessible starting materials and catalysts.     

Photocycloaddition Reactions of Alkyl and Aryl 2‐Thioxo‐3H‐benzoxazole‐ 3‐carboxylates to Alkenes

The photochemical reactions of alkyl and aryl 2‐thioxo‐3H‐benzoxazole‐3‐carboxylates 1 have been examined. Irradiation of 1 in the presence of tetra‐ and trisubstituted alkenes 2a and 2b , 2‐methylprop‐2‐ene nitrile 2e , and dienes 2f and 2g gave [2+2] cycloadducts of the CS bond of 2‐thioxobenzoxazoles and the CC bond of alkenes, spiro[benzoxazole‐thietanes] 3, 4, 8 – 13, 15, 18, 20, 23 – 26 in moderate‐to‐good yields. The photoaddition reactions proceed in a regiospecific manner. The spirocyclic compounds obtained are indefinitely stable at room temperature. Irradiation of 1a in the presence of 1,1‐ and 1,2‐disubstituted alkenes 2c and 2d yielded the products 5 – 7 of oxazole‐ring cleavage. Compound 1d also underwent photoaddition with alkenes to yield spiro[benzoxazole‐thietanes] and/or 2‐substituted benzoxazoles and/or iminothietanes, depending on the nature of the substituents present in the alkenes. On intramolecular [2+2] photoadduct, tetracyclic 27 , was obtained, when ethenyl 2‐thioxobenzoxazole‐3‐carboxylate 1e was irradiated.     

Simple synthesis of 2‐amino‐4‐(het)aryl‐4,6‐dihydro‐1(3)(11)H‐[1,3,5]triazino[2,1‐b]quinazolin‐6‐ones

The 2‐amino‐4‐(het)aryl‐4,6‐dihydro‐1(3)(11)H‐[1,3,5]triazino[2,1‐b]quinazolin‐6‐ones were prepared readily by cyclocondensation of anthranilic acid derived 4‐oxo‐3,4‐dihydroquinazolinyl‐2‐guanidine with a variety of aldehydes. The structures of the compounds were confirmed by nmr spectroscopy, including 2D NOESY experiments.     

Synthesis of new benzo[h]‐ and benzo[f]chromeno[2,3‐b]‐pyridine‐5‐ones

A number of new benzo[h]‐ and benzo[f]chromeno[2,3‐b] pyridine‐5‐ones derivatives were synthesized from benzo[h]‐ and benzo[f]‐chromone‐carbonitriles and amino‐benzo[h]‐ and benzo[f]chromone‐carbaldehydes. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:2–7, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20152     

Visible‐Light Photocatalytic Radical Alkenylation of α‐Carbonyl Alkyl Bromides and Benzyl Bromides

Through the use of [Ru(bpy)₃Cl₂] (bpy=2,2′‐bipyridine) and [Ir(ppy)₃] (ppy=phenylpyridine) as photocatalysts, we have achieved the first example of visible‐light photocatalytic radical alkenylation of various α‐carbonyl alkyl bromides and benzyl bromides to furnish α‐vinyl carbonyls and allylbenzene derivatives, prominent structural elements of many bioactive molecules. Specifically, this transformation is regiospecific and can tolerate primary, secondary, and even tertiary alkyl halides that bear β‐hydrides, which can be challenging with traditional palladium‐catalyzed approaches. The key initiation step of this transformation is visible‐light‐induced single‐electron reduction of C? Br bonds to generate alkyl radical species promoted by photocatalysts. The following carbon? carbon bond‐forming step involves a radical addition step rather than a metal‐mediated process, thereby avoiding the undesired β‐hydride elimination side reaction. Moreover, we propose that the Ru and Ir photocatalysts play a dual role in the catalytic system: they absorb energy from the visible light to facilitate the reaction process and act as a medium of electron transfer to activate the alkyl halides more effectively. Overall, this photoredox catalysis method opens new synthetic opportunities for the efficient alkenylation of alkyl halides that contain β‐hydrides under mild conditions.     

Synthesis and Bioassay of Novel Substituted Pyrano[2,3‐f]cinnoline‐2‐ones

A new series of 9‐substituted‐4,10‐dimethylpyrano[2,3‐f]cinnolin‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m ) were synthesized via intramolecular cyclization of the respective acyl amidrazone derivatives ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m ), catalyzed by polyphosphoric acid. Compounds ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m ) were synthesized through direct interaction of coumarin‐7‐yl hydrazonoyl chloride ( 3 ) with the corresponding cyclic sec‐amines in the presence of triethylamine. The structures of the new compounds were confirmed by elemental analyses, NMR, and MS spectral data. The antitumor activity of compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j , 5k , 5l , 5m was evaluated in vitro on breast cancer cell line (MCF‐7) by a cell viability assay utilizing the tetrazolium dye 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide. Among the compounds tested, compounds 5d , 5f , 5k , and 5h showed potential anti‐MCF‐7 activity and were able to reduce the viability after 72 h to less than 50%.     

Selective synthesis of some 4,5‐dihydro‐2H‐benzo[g]indazoles and 8,9‐dihydro‐2H‐benzo[e]indazoles via the vilsmeier‐haack reaction under thermal and microwave assisted conditions

A selective and easy method is described for the synthesis of 4,5‐dihydro‐2H‐benzo[g]indazoles and 8,9‐dihydro‐2H‐benzo[e]indazoles by the Vilsmeier‐Haack reaction of various tetralone phenylhydrazones under thermal and microwave irradiation conditions.     

Synthesis and characterization of substituted (benzo[b]thiophen‐2‐yl)‐4‐methyl‐4,5‐dihydro‐1H‐imidazol‐5‐ones

Reactions of 3‐chlorobenzo[b]thiophene‐2‐carbonyl chloride with 2‐alkyl‐2‐aminopropanamides have been used to prepare a series of carboxamides 1a‐d (yields 61‐85%). The products were submitted to base‐catalysed ring closure reactions to give the corresponding 4,5‐dihydro‐1H‐imidazol‐5‐ones 2a‐d (yields 69‐97%). By N‐methylation and N‐benzylation were prepared the corresponding 1‐alkyl derivatives 3a (91%) and 3b (85%). These two alkyl derivatives were studied from the standpoint of potential replacement of 3‐chlorine substituent by piperidine via the Buchwald‐Hartwig reaction. It was found that the reaction gives besides except required products of C‐N coupling 5a (14%) and 5b (12%) also products of reductive dechlorination 4a (max. 57%) and 4b (max. 56%). The reductive dechlorination product 4a is formed exclusively (42%) if butyl‐di‐(1‐adamantyl)phosphine (BDAP) is used.     

Efficient Organocatalytic Construction of C4‐Alkyl Substituted Piperidines and Their Application to the Synthesis of (+)‐α‐Skytanthine

Chiral piperidines which contain an alkyl group at C4 positions are one of the important architectures because it is appeared in several natural products. An efficient protocol for the preparation of C4‐alkyl substituted chiral piperidines using secondary amine catalyzed formal aza [3+3] cycloaddition reaction with aliphatic α,β‐unsaturated aldehydes and thiomalonamate derivatives is reported. In our reaction system, thiomalonamate is an excellent nucleophile and the addition of suitable acid and its amount is an important factor for the acceleration effect in organocatalytic reaction. Furthermore, water and MeOH also have an acceleration effect. These efforts lead to only 0.1 mol % catalyst loading in multigram scale synthesis for suitable reaction time. In addition, the efficient enantioselective total synthesis of (+)‐α‐skytanthine by using our developed reaction as key step was achieved in total 15 % yield. All carbon and nitrogen units were introduced by one step with high enantioselectivity.     

One‐Pot Synthesis of 3‐Alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones by the Reactions of 2‐(Azidomethyl)benzoates with NaH

A new and facile method for the general preparation of 3‐alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones has been developed. Thus, the reaction of 2‐(azidomethyl)benzoates with NaH affords, after workup with H₂O, 3‐alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones 2 . 2‐Substituted 3‐alkoxy‐2,3‐dihydro‐1H‐isoindol‐1‐ones 4 can be obtained by adding alkyl halides prior to workup with H₂O.     

Synthesis and Antioxidant Evaluation of Quinoxalino[2′,3′:5,6][1,3,4]thiadiazino[2,3‐b]quinazolin‐15‐ones: Derivatives of a Novel Ring System

Quinoxalino[2′,3′:5,6][1,3,4]thiadiazino[2,3‐b]quinazolin‐15‐one, a novel fused heterocyclic system, was synthesized from a one‐pot condensation reaction of 2,3‐dichloroquinoxaline and 3‐amino‐2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐one under mild condition. Derivatization was performed on treatment of the titled compound with several alkyl bromides. In vitro antioxidant activity of the synthesized compounds was evaluated.     

Synthesis of Pyrano[3,2‐b]indole Derivatives Based on Intramolecular Hetero‐Diels?Alder of 2‐Benzylidene‐2,3‐dihydro‐1H‐indol‐3‐ones

Pyrano[3,2‐b]indole derivatives 2 – 6 were synthesized in good yields from 1‐acetyl‐2‐benzylidene‐2,3‐dihydro‐1H‐indol‐3‐ones 8 and 13 – 15 by an intramolecular hetero‐Diels? Alder reaction. The structures of compounds 2a, 3a, 4, 5 , and 6 were unambiguously established by X‐ray analysis. Compounds 4 and 5 were further aromatized to the corresponding derivatives 16 and 17 , respectively.     

Reactions between arylhydrazinium chlorides and 2‐chloroquinoline‐3‐carbaldehydes: molecular and supramolecular structures of a hydrazone,a 4,9‐dihydro‐1H‐pyrazolo[3,4‐b]quinoline and two 1H‐pyrazolo[3,4‐b]quinolines

Hydrazone derivatives exhibit a wide range of biological activities, while pyrazolo[3,4‐b]quinoline derivatives, on the other hand, exhibit both antimicrobial and antiviral activity, so that all new derivatives in these chemical classes are potentially of value. Dry grinding of a mixture of 2‐chloroquinoline‐3‐carbaldehyde and 4‐methylphenylhydrazinium chloride gives (E)‐1‐[(2‐chloroquinolin‐3‐yl)methylidene]‐2‐(4‐methylphenyl)hydrazine, C₁₇H₁₄ClN₃, (I), while the same regents in methanol in the presence of sodium cyanoborohydride give 1‐(4‐methylphenyl)‐4,9‐dihydro‐1H‐pyrazolo[3,4‐b]quinoline, C₁₇H₁₅N₃, (II). The reactions between phenylhydrazinium chloride and either 2‐chloroquinoline‐3‐carbaldehyde or 2‐chloro‐6‐methylquinoline‐3‐carbaldehyde give, respectively, 1‐phenyl‐1H‐pyrazolo[3,4‐b]quinoline, C₁₆H₁₁N₃, (III), which crystallizes in the space group Pbcn as a nonmerohedral twin having Z′ = 3, or 6‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]quinoline, C₁₇H₁₃N₃, (IV), which crystallizes in the space group R. The molecules of compound (I) are linked into sheets by a combination of N—H…N and C—H…π(arene) hydrogen bonds, and the molecules of compound (II) are linked by a combination of N—H…N and C—H…π(arene) hydrogen bonds to form a chain of rings. In the structure of compound (III), one of the three independent molecules forms chains generated by C—H…π(arene) hydrogen bonds, with a second type of molecule linked to the chains by a second C—H…π(arene) hydrogen bond and the third type of molecule linked to the chain by multiple π–π stacking interactions. A single C—H…π(arene) hydrogen bond links the molecules of compound (IV) into cyclic centrosymmetric hexamers having (S₆) symmetry, which are themselves linked into a three‐dimensional array by π–π stacking interactions.     

Interaction of 3‐(2‐Aminophenyl)‐6‐R1‐1,2,4‐triazin‐5‐ones with Acylating Reagents: An Efficient Method for Preparation of 6‐Substituted 3‐R1‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐ones

The series of 6‐substituted 3‐R¹‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐one was prepared via condensation of 3‐(2‐aminophenyl)‐6‐R¹‐1,2,4‐triazin‐5‐ones with acylating reagents. Particularities of ¹H NMR spectra have been also discussed based on the comparison of experimental and theoretical results for 3‐methyl‐6‐phenyl‐2H‐[1,2,4]triazino[2,3‐c]quinazolin‐2‐one and its 4,3‐isomer.     

Pyranopyrazoles III synthesis of 1H‐pyrano[2,3‐c]pyrazol‐4‐ones

Various derivatives of title ring system were synthesized by Claisen condensation of 4 acetyl‐5 ‐hydroxy‐pyrazoles with appropriate esters, followed by acid‐catalyzed ring closure.