Synthesis of 4-substituted imidazo[1,2-a]quinoxalines

A concise approach to 4-substituted imidazo[1,2-a]quinoxalines 7 is described, starting from 1-fluoro-2-nitrobenzene ( 3 ). The high variability in the functionalization of the imidazo [1,2-a]quinoxaline-4-position is due to the easy introduction of these substituents by N-acylation in the second last step.     

4-H-吡唑[1,5-a]苯并咪唑的合成

以2-卤苯胺和乙氧基亚甲基丙二腈为原料通过重氮化、酰化和碱性环合得到1-芳基-4-氰基-5-胺基吡唑,再经过Ullmann偶联制得标题化合物。产物结构经1HNMR、13CNMR、IR和元素分析表征。     

Iron(III)‐Catalyzed Cascade Reaction between Nitroolefins and 2‐Aminopyridines: Synthesis of Imidazo[1,2‐a]pyridines and Easy Access towards Zolimidine

The iron(III)‐catalyzed one‐pot cascade reaction between nitroolefins and 2‐aminopyridines has been demonstrated for the synthesis of imidazo[1,2‐a]pyridines by exploiting the bielectrophilic nature of nitroolefins. This methodology could be successfully applicable for the synthesis of zolimidine, a useful drug for the treatment of peptic ulcer. The reaction proceeds through Michael addition followed by intramolecular cyclization and in situ denitration.     

7-羟甲基咪唑并[1,2-a]吡啶的合成

以6-氨基-3-吡啶甲酸为起始原料,经过酯化反应、环合反应、还原反应得到7-羟甲基咪唑并[1,2-a]吡啶,总收率为42％.     

咪唑并[1,2-a]吡啶化合物的简便合成

以2-氨基-3-羟基吡啶为原料,经过一锅两步反应合成了12个咪唑并[1,2-a]吡啶类化合物。2-氨基-3-羟基吡啶与N,N-二甲基甲酰胺二甲基缩醛进行反应,几乎定量得到(E)-N'-(3-羟基吡啶-2-基)-N,N-二甲基甲脒中间体,然后在Na HCO3作用下,于一锅中和活泼亲电化合物(溴乙酸乙酯、溴乙腈和2-溴代苯乙酮)发生合成咪唑环的反应及羟基上的取代反应,以50.3%~85.2%的总收率得到目标产物。该一锅两步方法具有原料易得、反应时间短、操作简便、收率高等优点。     

Facile Palladium‐Catalyzed Synthesis of 3‐Arylpyrazolo[1,5‐a]pyrimidines

An efficient palladium‐catalyzed synthesis of 3‐arylpyrazolo[1,5‐a]pyrimidines has been investigated. The key step in the synthesis is a Suzuki biaryl coupling of 3‐bromo‐2,5‐dimethyl‐7‐aminopyrazolo[1,5‐a]pyrimidines with arylboronic acids to provide 3‐arylpyrazolo[1,5‐a]pyrimidines in moderate to good yield. The synthetic utility of this methodology has been demonstrated by a concise and convergent synthesis of R121920, a potent CRHR₁ antagonist recently undergoing clinical evaluations.     

Multicomponent Syntheses based upon Copper‐Catalyzed Alkyne‐Azide Cycloaddition

The copper‐catalyzed alkyne‐azide cycloaddition (CuAAC) is a highly versatile, regioselective synthesis of 1,4‐disubstituted 1,2,3‐triazoles under mild reaction conditions and has found numerous applications in medicinal, bioorganic, and materials chemistry in the past one and a half decades. By virtue of the enormous tolerance for functional groups and the mild reaction conditions, CuAAC has become increasingly important in combination with multicomponent reactions (MCR), either in a domino or in a consecutive fashion. While the majority of CuAAC‐based MCR are founded on the in situ or en route generation of azides, one‐pot generation of alkynes and the concatenation with other MCR are rapidly catching up and novel sequences for efficient one‐pot syntheses of triazole‐based structures in a multicomponent fashion are constantly evolving. This review summarizes important contributions of CuAAC‐based MCR including MCR‐type applications in polymer science.

     

Copper‐Catalyzed Domino Synthesis of Benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones using Cyanamide as a Building Block

An efficient and practical copper‐catalyzed domino synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones has been developed. The protocol uses N‐(2‐halophenyl)‐3‐alkylpropiolamides and cyanamide as the starting materials, inexpensive copper(I) iodide and pipecolinic acid as the catalyst and ligand, and the corresponding products were obtained in moderate to good yields.

     

Copper‐Catalyzed Synthesis of Imidazo[1,2‐a]pyridines through Tandem Imine Formation‐Oxidative Cyclization under Ambient Air: One‐Step Synthesis of Zolimidine on a Gram‐Scale

A new copper‐catalyzed oxidative cyclization via C H amination between 2‐aminopyridines and methyl aryl/heteroaryl ketones has been developed under ambient air. Imidazo[1,2‐a]pyridines containing a wide range of functional groups have been synthesized from basic and easily available starting materials. This simple, one‐pot reaction protocol is applicable for the direct preparation of zolimidine (a marketed antiulcer drug) on a large scale.     

Brønsted Acid‐Catalyzed Four‐Component Cascade Reaction: Facile Synthesis of Hexahydroimidazo[1,2‐a]pyridines

An efficient four‐component cascade reaction for the synthesis of trisubstituted hexahydroimidazo[1,2‐a]pyridines starting from readily available aldehydes, ketones and ethane‐1,2‐diamine catalyzed by p‐toluenesulfonic acid is described. Two new cycles and five new bonds are constructed with all reactants being efficiently utilized in this transformation. The mechanism of the reaction was investigated and some crucial reaction intermediates were observed.     

Gold‐Catalyzed Redox Synthesis of Imidazo[1,2‐a]pyridines using Pyridine N‐Oxide and Alkynes

A mild, catalytic, atom economical synthesis of imidazo[1,2‐a]pyridines has been developed: catalytic dichloro(2‐pyridinecarboxylato)gold [PicAuCl₂] in the presence of an acid produces a range of imidazo[1,2‐a]pyridines in good yields starting from alkynes and 2‐aminopyridine N‐oxides. This strategy is mild and foreseen to be of particular use for the installation of stereogenic centers adjacent to the imidazo[1,2‐a]pyridine ring without loss of enantiomeric excess.

     

An Efficient Tetrabutylammonium Fluoride (TBAF)‐Catalyzed Three‐Component Synthesis of 3‐Substituted Indole Derivatives under Solvent‐Free Conditions

An expedient and efficient one‐pot three‐component synthesis of 3‐substituted indoles has been developed by the reaction of indoles, active methylene compounds and aldehydes using a catalytic amount of tetrabutylammonium fluoride under solvent‐free conditions.     

Efficient One-Pot Synthesis of Tetrahydrobenzo[b]pyrans by Ethylenediamine Diacetate-Catalyzed Multicomponent Reaction Under Solvent-Free Conditions

Ethylenediamine diacetate is found to be an efficient catalyst for the multicomponent condensation reaction of dimedone, aldehydes, and malononitrile to afford the corresponding tetrahydrobenzo[b]pyrans in good yields. The remarkable features of this new procedure are high yields, short reaction times, simple experimental and work-up procedures, mild and environmentally friendly reaction conditions, and economic availability of the catalyst.     

Copper‐Mediated Tandem C(sp2)–H Sulfenylation and Annulation of Arenes with 2‐Mercaptoimidazoles: Regio‐ and Site‐selective Access to Polycyclic Fused Imidazo[2,1‐b][1,3]thiazinones

An efficient copper‐mediated tandem C(sp²)–H sulfenylation and annulation of arenes with 2‐mercaptoimidazoles to provide polycyclic fused imidazo[2,1‐b][1,3]thiazinones has been developed. This tandem reaction is likely initiated by C(sp²)–H thiolation of benzamide with 2‐mercaptoimidazole followed by intramolecular nucleophilic substitution of the amide carbonyl group. A notable feature of this reaction is that it can afford rather complex products in a single synthesis step from easily accessible starting materials using amide‐oxazoline as a removable bidentate directing group. A variety of benzamides and 2‐mercaptoimidazoles bearing different substituents are compatible with this transformation.

     

4,5,6,7-四氢吡唑并[1,5-a]哌嗪-3-甲酸乙酯的合成

以4-氯-3-氧代丁酸乙酯为原料,经与叔丁醇钾醚化、DMF-DMA缩合、水合肼环合、脱叔丁基、羟基氧化、还原氨化、分子内环合以及氢化脱苄等反应合成了标题化合物。并对其中关键的羟基氧化反应和分子内环化反应的工艺条件进行了优化,获得了较优的工艺条件:在羟基氧化反应中以二氧化锰为氧化剂、氯仿为溶剂;在分子内环化反应中以甲基磺酰氧基(OMs)为离去基团。目标化合物的总收率为39.5%,其结构经~1HNMR、~(13)CNMR、MS和元素分析进行了确定。     

Vanadyl Acetylacetonate Catalyzed Methylenation of Imidazo[1,2‐a]pyridines by Using Dimethylacetamide as a Methylene Source: Direct Access to Bis(imidazo[1,2‐a]pyridin‐3‐yl)methanes

An efficient protocol has been developed for the methylenation of imidazo[1,2‐a]pyridines using dimethylacetamide (DMA) as methylene source in the presence of vanadyl acetylacetonate [VO(acac)₂] as the catalyst and iodobenzene diacetate as the oxidant. The reaction involves coupling of sp³‐ and sp²‐hybridized carbons and proceeds through the formation of an iminium ion. A wide variety of imidazo[1,2‐a]pyridines were converted to bis(imidazo[1,2‐a]pyridin‐3‐yl)methanes in good to excellent yields. A gram‐scale reaction demonstrated the potential for the scale‐up processes.

     

Regioselective Copper‐Catalyzed Oxidative Cross‐Coupling of Imidazo[1,2‐a]pyridines with Methyl Ketones: An Efficient Route for Synthesis of 1,2‐Diketones

An efficient copper‐catalyzed oxidative coupling of imidazo[1,2‐a]pyridines with methyl ketones to directly generate structurally sophisticated 1,2‐dicarbonyl imidazo[1,2‐a]pyridine derivatives under oxidative conditions is described. The reaction proceeds in good yields using the environmental friendly molecular oxygen as the oxidant. ¹⁸O‐Labelling experiments unambiguously established that the oxygen of the dicarbonyl products originated from oxygen rather than from water.

     

Syntheses and biological activities of novel diheterocyclic compounds containing 1,2,4‐triazolo[1,5‐a]pyrimidine and 1,3,4‐oxadiazole

In a search for novel agrochemicals with high activity and low toxicity, a series of diheterocyclic compounds containing 1,2,4‐triazolo[1,5‐a]pyrimidine and 1,3,4‐oxadiazole rings were designed and synthesized by a four‐step synthetic route starting from 2‐mercapto‐5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine. The structures of all the compounds synthesized were confirmed by ¹H NMR, mass spectroscopy and elemental analysis. The preliminary bioassay against Brassica campestris L and Echinochloa crusgalli Beavu indicated that the title compounds displayed herbicidal activity at the concentration of 100 ppm and that compounds 5a (R = CH₃), 5d (R = C₂H₅) and 5f (R = i‐Bu) were found to have particularly high activities. In addition, the results of an in vivo test at a concentration of 50 ppm showed that all the compounds prepared were highly active against Rhizoctonia slain, but not active against Fusarium oxysporum, Gibberella zeave and Phoma sparagi. A further in vivo test showed that compound 5j possessed better fungicidal activity against Rhizoctonia solani at a concentration of 200 ppm than Carbendazim and Validamycin A, which are well known for their fungicidal activity against Rhizoctonia solani. To our knowledge, this is the first report that 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives display fungicidal activity against Rhizoctonia solani. © 2001 Society of Chemical Industry     

Gold‐Catalyzed Synthesis of 3‐Acylimidazo[1,2‐a]pyridines via Carbene Oxidation

A convenient gold‐catalyzed strategy for the synthesis of imidazo[1,2‐a]pyridine derivatives has been developed via gold carbene complexes. This transformation opens a new synthetic route to a variety of 3‐carbonyl‐substituted imidazo[1,2‐a]pyridines using air as oxidant affording the products in good yields.

     

Synthesis of Chiral N‐Sulfonyl and N‐Phosphinoyl α‐Halo Aldimine Precursors

α‐Halogenated aldimines have emerged as an important class of synthetic intermediates. The stability and reactivity of α‐halo aldimines can vary greatly depending on the nitrogen protecting group. A general synthesis of stable, chiral α‐halo‐N‐sulfonyl and N‐phosphinoyl aldimine precursors is presented (42–96% yield). The corresponding α‐halo aldimines can be isolated upon treatment with a mild base. Enantioenriched α‐chloro aldehydes can be employed to afford aldimine precursors with no erosion of optical purity. Both the enantioenriched aldimine precursor and the isolated aldimine can react with an alkynyllithium nucleophile to give trans‐β‐chloroamine products with excellent dr. Ring closure affords the enantioenriched trans‐aziridine, demonstrating the potential for this approach in complex molecule synthesis.