- An improved synthesis of pyridine-thiazole cores of thiopeptide antibiotics
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(Figure Presented) The oxidation of 2-methylthiazoles to 2-formylthiazoles simplifies the implementation of the Bagley variant of the Bohlmann-Rahtz reaction as a key step in a concise new route to pyridine cores of thiopeptide antibiotics.
- Aulakh, Virender S.,Ciufolini, Marco A.
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Read Online
- A simple continuous flow microwave reactor
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A new simple procedure for microwave-assisted organic synthesis under continuous flow processing has been developed for use in a monomodal microwave synthesizer with direct temperature control using the instrument's in-built IR sensor. This design makes optimum use of the standing wave cavity to improve the energy efficiency of microwave-assisted flow reactions.
- Bagley, Mark C.,Jenkins, Robert L.,Lubinu, M. Caterina,Mason, Christopher,Wood, Robin
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Read Online
- Microscale Parallel Synthesis of Acylated Aminotriazoles Enabling the Development of Factor XIIa and Thrombin Inhibitors
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Herein we report a microscale parallel synthetic approach allowing for rapid access to libraries of N-acylated aminotriazoles and screening of their inhibitory activity against factor XIIa (FXIIa) and thrombin, which are targets for antithrombotic drugs. This approach, in combination with post-screening structure optimization, yielded a potent 7 nM inhibitor of FXIIa and a 25 nM thrombin inhibitor; both compounds showed no inhibition of the other tested serine proteases. Selected N-acylated aminotriazoles exhibited anticoagulant properties in vitro influencing the intrinsic blood coagulation pathway, but not extrinsic coagulation. Mechanistic studies of FXIIa inhibition suggested that synthesized N-acylated aminotriazoles are covalent inhibitors of FXIIa. These synthesized compounds may serve as a promising starting point for the development of novel antithrombotic drugs.
- Platte, Simon,Korff, Marvin,Imberg, Lukas,Balicioglu, Ilker,Erbacher, Catharina,Will, Jonas M.,Daniliuc, Constantin G.,Karst, Uwe,Kalinin, Dmitrii V.
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supporting information
p. 3672 - 3690
(2021/08/07)
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- Green synthesis method of nicotinic acid ester compounds based on non-metallic conditions
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The invention discloses a green synthesis method based on nicotinic acid ester compounds under non-metallic conditions, and belongs to the technical field of organic synthesis. The method comprises the following steps of (III) replacing cyclopropanol and (II) substituted enamine ester as a raw material, taking tetramethyl piperidine nitrogen oxide as an oxidizing agent, 110 - 130 °C, stirring and reacting in an organic solvent to synthesize a (I) nicotinate compound. The invention provides a green synthesis method based on nicotinic acid ester compounds under non-metallic conditions, wherein cyclopropanols and enamine esters are taken as raw materials, and a polysubstituted nicotinate is synthesized through a strategy of oxidative dehydrogenation of ketene cyclization.
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Paragraph 0079-0086; 0109-0112
(2021/09/29)
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- Development of novel isatin–nicotinohydrazide hybrids with potent activity against susceptible/resistant Mycobacterium tuberculosis and bronchitis causing–bacteria
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Joining the global fight against Tuberculosis, the world's most deadly infectious disease, herein we present the design and synthesis of novel isatin-nicotinohydrazide hybrids (5a–m and 9a–c) as promising anti-tubercular and antibacterial agents. The anti-tubercular activity of the target hybrids was evaluated against drug-susceptible M. tuberculosis strain (ATCC 27294) where hybrids 5d, 5g and 5h were found to be as potent as INH with MIC = 0.24 μg/mL, also the activity was evaluated against Isoniazid/Streptomycin resistant M. tuberculosis (ATCC 35823) where compounds 5g and 5h showed excellent activity (MIC = 3.9 μg/mL). Moreover, the target hybrids were examined against six bronchitis causing-bacteria. Most derivatives exhibited excellent antibacterial activity. K. pneumonia emerged as the most sensitive strain with MIC range: 0.49–7.81 μg/mL. Furthermore, a molecular docking study has proposed DprE1 as a probable enzymatic target for herein reported isatin-nicotinohydrazide hybrids, and explored the binding interactions within the vicinity of DprE1 active site.
- Elsayed, Zainab M.,Eldehna, Wagdy M.,Abdel-Aziz, Marwa M.,El Hassab, Mahmoud A.,Elkaeed, Eslam B.,Al-Warhi, Tarfah,Abdel-Aziz, Hatem A.,Abou-Seri, Sahar M.,Mohammed, Eman R.
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p. 384 - 393
(2021/01/13)
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- Synthesis method of pyridine-3-formate compound
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The invention discloses a synthesis method of a pyridine-3-formate compound, and belongs to the technical field of organic synthesis. The synthesis method comprises the following step: using an aminoalkenoate compound and an alpha, beta-saturated ketone compound or an alpha, beta-saturated aldehyde compound as raw materials, and performing one-pot multi-step serial reaction under the action of acatalyst, a ligand and an oxidant to obtain the pyridine-3-formate compound. The synthesis method has the advantages of simple and convenient operation, mild conditions, wide application range of a substrate, and the like, and is suitable for industrial production.
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Paragraph 0036-0038
(2018/04/03)
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- Synthesis of Functionalized Pyridines via Cu(II)-Catalyzed One-Pot Cascade Reactions of Inactivated Saturated Ketones with Electron-Deficient Enamines
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In this paper, a novel and efficient synthesis of 3-acylpyridines and pyridine-3-carboxylates through the oxidative one-pot sequential reactions of inactivated saturated ketones with electron-deficient enamines is presented. Mechanistically, the formation of the title compounds involves the in situ formation of an enone intermediate through an oxidative dehydrogenation of the saturated ketone substrate, followed by its [3+3] annulation with β-enaminone or β-enaminoester via a cascade process, including Michael addition, aldol type condensation, and oxidative aromatization.
- Chen, Guang,Wang, Ze,Zhang, Xinying,Fan, Xuesen
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p. 11230 - 11237
(2017/10/27)
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- Silver-Catalyzed Minisci Reactions Using Selectfluor as a Mild Oxidant
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A new method for silver-catalyzed Minisci reactions using Selectfluor as a mild oxidant is reported. Heteroarenes and quinones both participate in radical C-H alkylation and arylation from a variety of carboxylic and boronic acid radical precursors. Several oxidatively sensitive and highly reactive radical species are successful, providing structures that are challenging to access by other means.
- Galloway, Jordan D.,Mai, Duy N.,Baxter, Ryan D.
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supporting information
p. 5772 - 5775
(2017/11/10)
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- Protective effect of novel substituted nicotine hydrazide analogues against hypoxic brain injury in neonatal rats via inhibition of caspase
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In hypoxic-ischemic injury of the brain of neonates, the level of caspase-3 was found to be aberrantly activated. Its overexpression leads to the alteration of cytoskeleton protein fodrin and loss of DNA repair enzyme which ultimately results in neurological impairment and disability. Concerning this, the present study was intended to develop novel nicotine hydrazide analogues as caspase inhibitors via efficient synthetic route. These compounds were subsequently tested for inhibitory activity against caspase-3 and -7 where they exhibit highly potent activity against caspase-3 revealing compound 5k as most potent inhibitor (IC50 = 19.4 ± 2.5 μM). In Western blot analysis, 5k considerably inhibits the overexpression of caspase-3. The aryl nicotinate of compound 5k, as indicated by molecular docking was found to engage His121 and critical enzyme thiols, i.e., Cys163 of caspase-3 for its potent activity. Moreover, histopathological examination of brain tissues and hippocampus neurons showed that compound 5k considerably improves the brain injury and exert neuroprotective effects in hypoxic-ischemic (HI). In brain homogenate, 5k significantly improves the activity of MDA, SOD, GSH-Px, CAT and T-AOC to exert its beneficial effect against oxidative stress induced by HI injury.
- Deng, Chang-Bo,Li, Juan,Li, Lu-Yi,Sun, Feng-Jie
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supporting information
p. 3195 - 3201
(2016/06/13)
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- Consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz syntheses of tri- and tetrasubstituted pyridines
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The concatenation of the modified Sonogashira alkynone synthesis and the Bagley-Bohlmann-Rahtz pyridine synthesis gives novel consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz (cBBR) syntheses of tri- and tetrasubstituted pyridines in a one-pot fashion. With these processes 15 differently substituted 3-ethoxycarbonyl 2-methylpyridines can be readily obtained in modest to moderate yields.
- Dohe, Janis,Müller, Thomas J. J.
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p. 705 - 718
(2016/07/06)
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- Mannich bases as enone precursors for water-mediated efficient synthesis of 2,3,6-trisubstituted pyridines and 5,6,7,8-tetrahydroquinolines
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A highly efficient, regioselective, and environmentally friendly method has been developed for water-mediated synthesis of 2,3,6-trisubstituted pyridines and 5,6,7,8-tetrahydroquinolines. The introduced method allows easy preparation of various polysubstituted pyridines and 5,6,7,8-tetrahydroquinolines via domino reaction of an enolizable ketone, ammonia and enones derived from different Mannich bases in mild reaction conditions. Montmorillonite K-10 promoted this one-pot three-component reaction and gave both new and known 2,3,6-trisubstituted pyridines and 5,6,7,8-tetrahydroquinolines in good yields. The reaction protocol provides a wide array of functionality in construction of polysubstituted pyridines and 5,6,7,8-tetrahydroquinolines from commercially available starting materials in easily applicable and environmentally friendly conditions.
- Hanashalshahaby, Essam Hamied Ahmed,Unaleroglu, Canan
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supporting information
p. 374 - 380
(2015/06/22)
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- Cu-Catalyzed Three-Component Cascade Annulation Reaction: An Entry to Functionalized Pyridines
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A concise copper-catalyzed N-O bond cleavage/C-C/C-N bond formation procedure has been described for the synthesis of multisubstituted pyridines. Various oxime acetates, activated methylene compounds, and a wide range of aldehydes bearing aryl, heteroaryl, vinyl, and trifluoromethyl groups were employed to provide the tri- or tetrasubstituted pyridines with flexible substitution patterns. Moreover, this method features inexpensive catalysts, no need for extra oxidant, and high step-enconomy, which make it pratical and attractive.
- Jiang, Huanfeng,Yang, Jidan,Tang, Xiaodong,Li, Jianxiao,Wu, Wanqing
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p. 8763 - 8771
(2015/09/15)
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- Visible-light-promoted iminyl-radical formation from Acyl oximes: A unified approach to pyridines, quinolines, and phenanthridines
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A unified strategy involving visible-light-induced iminyl-radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac-[Ir(ppy)3] as a photoredox catalyst, the acyl oximes were converted by 1 e- reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N-containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible-light-induced iminyl-radical formation was successfully applied to a five-step concise synthesis of benzo[c]phenanthridine alkaloids.
- Jiang, Heng,An, Xiaode,Tong, Kun,Zheng, Tianyi,Zhang, Yan,Yu, Shouyun
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supporting information
p. 4055 - 4059
(2015/03/30)
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- Design, synthesis and antitubercular activity of certain nicotinic acid hydrazides
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Three series of 6-Aryl-2-methylnicotinohydrazides 4a-i, N'-Arylidene-6-(4-bromophenyl)-2-methylnicotino hydrazides 7a-f, and N'-(un/substituted 2-oxoindolin-3-ylidene)-6-(4-fluorophenyl)-2-methylnicotinohydrazides 8a-c were synthesized and evaluated for their potential in vitro antimycobacterial activity against M.Tuberculosis. The results showed that isatin hydrazides 8a-c are remarkably more active than the parent hydrazide 4c. Hydrazides 8b and 8c exhibited the highest activity among all the tested compounds (MIC = 12.5 and 6.25 μg/mL, respectively). Compounds 8b and 8c were also devoid of apparent cytotoxicity to HT-29, PC-3, A549, HepG2 and MCF-7 cancer cell lines. Besides, 8b and 8c showed good drug-likeness scores of 0.62 and 0.41, respectively. Those two isatin hydrazides could offer an excellent framework for future development to obtain more potent antitubercular agents. The SAR study suggested that lipophilicity of the synthesized derivatives is a crucial element that accounts for their antimycobacterial activity. Finally, a theoretical kinetic study was established to predict the ADME of the active derivatives.
- Eldehna, Wagdy M.,Fares, Mohamed,Abdel-Aziz, Marwa M,Abdel-Aziz, Hatem A
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p. 8800 - 8815
(2016/09/04)
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- Design, synthesis and QSAR study of certain isatin-pyridine hybrids as potential anti-proliferative agents
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A hybrid pharmacophore approach was adopted to design and synthesize new series of isatin-pyridine hybrids. All the newly prepared hybrids (5a-o, 8 and 11a-d) were in vitro evaluated for their anti-proliferative activity against three human cancer cell lines, namely HepG2 hepatocellular carcinoma, A549 lung cancer and MCF-7 breast cancer. Compound 8 emerged as the most active member against HepG2 cell line (ICinf50/inf = 2.5 ± 0.39 μM), with 2.7-fold increased activity than the reference drug, doxorubicin (ICinf50/inf = 6.9 ± 2.05 μM). Whilst, compound 11c was found to be the most potent counterpart against A549 and MCF-7 cell lines with ICinf50/inf values of 10.8 ± 1.15 and 6.3 ± 0.79, respectively. The weightiness of the utilization of non-cleavable linker, as the chalcone linker, and simplification of the first group, was explored via the SAR study. Furthermore, a QSAR model was built to explore the structural requirements controlling the cytotoxic activities. Notably, the predicted activities by the QSAR model were very close to those experimentally observed, hinting that this model could be safely applied for prediction of more efficacious hits comprising the same skeletal framework. Finally, a theoretical kinetic study was established to predict the ADME of the active hybrids.
- Eldehna, Wagdy M.,Altoukhy, Ayman,Mahrous, Hoda,Abdel-Aziz, Hatem A.
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p. 684 - 694
(2015/02/02)
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- Transition-metal-free synthesis of substituted pyridines via ring expansion of 2-allyl-2H-azirines
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A new strategy to open the 2-allyl-2H-azirines by 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) promotion in metal-free conditions affording 1-azatrienes that in situ electrocyclize to the pyridines in good to excellent yields is reported. The reaction displays a broad substrate scope and good tolerance to a variety of substituents including aryl, alkyl, and heterocyclic groups. In addition, one-pot synthesis of pyridines from oximes via in situ formation of 2H-azirines was achieved.
- Jiang, Yaojia,Park, Cheol-Min,Loh, Teck-Peng
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supporting information
p. 3432 - 3435
(2014/07/21)
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- One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor
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The Bohlmann-Rahtz pyridine synthesis and the Hantzsch dihydropyridine synthesis can be carried out in a microwave flow reactor or using a conductive heating flow platform for the continuous processing of material. In the Bohlmann-Rahtz reaction, the use of a Bronsted acid catalyst allows Michael addition and cyclodehydration to be carried out in a single step without isolation of intermediates to give the corresponding trisubstituted pyridine as a single regioisomer in good yield. Furthermore, 3-substituted propargyl aldehydes undergo Hantzsch dihydropyridine synthesis in preference to Bohlmann-Rahtz reaction in a very high yielding process that is readily transferred to continuous flow processing.
- Bagley, Mark C.,Fusillo, Vincenzo,Jenkins, Robert L.,Lubinu, M. Caterina,Mason, Christopher
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supporting information
p. 1957 - 1968
(2013/10/22)
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- IBX mediated reaction of β-enamino esters with allylic alcohols: A one pot metal free domino approach to functionalized pyridines
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IBX facilitated the reaction of β-enamino esters with allylic alcohols affording a direct, one-pot and metal free synthesis of functionalized pyridines including 2-substituted nicotinic acids, densely substituted pyridines and precursors of azafluorenones. The methodology also afforded the racemic pyridine core of cyclothiazomycin.
- Gade, Narendar Reddy,Devendram,Pal, Manojit,Iqbal, Javed
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supporting information
p. 7926 - 7928
(2013/09/02)
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- Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity
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Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC 50 range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F3 and F4) and two Aromatic annotations (F1 and F2).
- Abdel-Aziz, Hatem A.,Aboul-Fadl, Tarek,Al-Obaid, Abdul-Rahman M.,Ghazzali, Mohamed,Al-Dhfyan, Abdullah,Contini, Alessandro
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p. 1543 - 1552
(2013/03/13)
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- Bohlmann-Rahtz cyclodehydration of aminodienones to pyridines using N-iodosuccinimide
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Cyclodehydration of Bohlmann-Rahtz aminodienone intermediates using N-iodosuccinimide as a Lewis acid proceeds at low temperature under very mild conditions to give the corresponding 2, 3,6-trisubstituted pyridines in high yield and with total regiocontrol.
- Bagley, Mark C.,Glover, Christian
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experimental part
p. 3211 - 3227
(2010/09/04)
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- Continuous flow processing from microreactors to mesoscale: The Bohlmann-Rahtz cyclodehydration reaction
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The cyclodehydration of a number of Bohlmann-Rahtz aminodienones exemplifies the use of continuous flow processing to transfer operations from commercial microreactors and microwave batch reactors to mesoscale production using different technology platforms, including a microwave flow reactor.
- Bagley, Mark C.,Fusillo, Vincenzo,Jenkins, Robert L.,Lubinu, M. Caterina,Mason, Christopher
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experimental part
p. 2245 - 2251
(2010/07/03)
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- Microwave-assisted regioselective one-pot synthesis of trisubstituted pyridine scaffolds using K5CoW12O40.3H 2O under solvent free conditions
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(Chemical Equation Presented) A highly efficient, microwave-assisted, regioselective synthesis of 2,3-disubstituted-6-arylpyridines and new series of 7,7-dimethyl-2-aryl-5,6,7,8-tetrahydroquinoline-5-ones from enaminones in the presence of K5CoW12O40.3H2O (1.0 mol %) as heterogeneous catalyst under solvent free conditions is reported.
- Kantevari, Srinivas,Chary, Mahankhali Venu,Vuppalapati, Srinivasu V. N.,Lingaiah
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p. 1099 - 1102
(2008/12/20)
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- Design and synthesis of 6-phenylnicotinamide derivatives as antagonists of TRPV1
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6-Phenylnicotinamide (2) was previously identified as a potent TRPV1 antagonist with activity in an in vivo model of inflammatory pain. Optimization of this lead through modification of both the biaryl and heteroaryl components has resulted in the discovery of 6-(4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5-yl)nicotinamide (32; SB-782443) which possesses an excellent overall profile and has been progressed into pre-clinical development.
- Westaway, Susan M.,Thompson, Mervyn,Rami, Harshad K.,Stemp, Geoffrey,Trouw, Leontine S.,Mitchell, Darren J.,Seal, Jon T.,Medhurst, Stephen J.,Lappin, Sarah C.,Biggs, James,Wright, James,Arpino, Sandra,Jerman, Jeffrey C.,Cryan, Jennifer E.,Holland, Vicky,Winborn, Kim Y.,Coleman, Tanya,Stevens, Alexander J.,Davis, John B.,Gunthorpe, Martin J.
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scheme or table
p. 5609 - 5613
(2009/06/18)
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- A highly efficient regioselective one-pot synthesis of 2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted tetrahydroquinolin-5-ones using K5CoW12O40·3H2O as a heterogeneous recyclable catalyst
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A systematic investigation into the regioselective one-pot, three-component condensation of enaminones 1a-g, β-dicarbonyl compounds 2a-c, and ammonium acetate in the presence of a catalytic amount of K5CoW12O40·3H2O (0.01 equiv or 1.0 mol %) under solvent free conditions, as well as in refluxing isopropanol, has been reported. The reaction was highly efficient to produce 2,3,6-trisubstituted pyridines 3a-g, 4a-g, and novel 2,7,7-trisubstituted-5,6,7,8-tetrahydroquinoline-5-ones 5a-g in excellent yields. The present procedure offers advantages of short reaction time, simple work-up, and the catalyst exhibited remarkable reusable activity.
- Kantevari, Srinivas,Chary, Mahankhali Venu,Vuppalapati, Srinivasu V.N.
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p. 13024 - 13031
(2008/03/14)
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- A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support
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A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support is described. A facile synthesis of 2,3-disubstituted-6-arylpyridines from enaminones using montmorillonite K10 as solid acid support is reported herein.
- Jagath Reddy,Latha,Thirupathaiah,Srinivasa Rao
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p. 301 - 302
(2007/10/03)
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- One-pot multistep Bohlmann-Rahtz heteroannulation reactions: Synthesis of dimethyl sulfomycinamate
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(Chemical Equation Presented) The synthesis of dimethyl sulfomycinamate, the acidic methanolysis product of the sulfomycin family of thiopeptide antibiotics, from methyl 2-oxo-4-(trimethylsilyl)but-3-ynoate is achieved in a 2,3,6-trisubstituted pyridine synthesis that proceeds with total regiocontrol in 13 steps by the Bohlmann-Rahtz heteroannulation of a 1-(oxazol-4-yl)enamine or in 12 steps and 9% yield by three-component cyclocondensation with N-[3-oxo-3-(oxazol-4-yl)propanoyl]serine and ammonia in ethanol.
- Bagley, Mark C.,Chapaneri, Krishna,Dale, James W.,Xiong, Xin,Bower, Justin
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p. 1389 - 1399
(2007/10/03)
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- Iodine-catalysed Bohlmann-Rahtz cyclodehydration reactions
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The cyclodehydration of Bohlmann-Rahtz aminodienones is catalysed by iodine in ethanol at room temperature to give 2,3,6-trisubstituted pyridines in excellent yield, with total regiocontrol and without the need for chromatographic purification.
- Bagley, Mark C.,Glover, Christian,Chevis, Duncan
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p. 649 - 651
(2007/10/03)
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- A new mild method for the one-pot synthesis of pyridines
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Polysubstituted pyridines are prepared in good yield and with total regiocontrol by the one-pot reaction of an alkynone, 1,3-dicarbonyl compound and ammonium acetate in alcoholic solvents. This new three-component heteroannulation reaction proceeds under mild conditions in the absence of an additional acid catalyst and has been used in the synthesis of dimethyl sulfomycinamate, the acidic methanolysis degradation product of the sulfomycin family of thiopeptide antibiotics.
- Xiong, Xin,Bagley, Mark C.,Chapaneri, Krishna
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p. 6121 - 6124
(2007/10/03)
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- New N-halosuccinimide-mediated reactions for the synthesis of pyridines
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5-Bromo-2,6-dialkylpyridine-4-carboxylates are generated in excellent yield by the Michael addition of enaminoesters and ethynyl ketones followed by bromocyclization using N-bromosuccinimide within 1 hour at 0°C. Treatment of the same aminopentadienone intermediates with N-iodosuccinimide facilitates a low temperature cyclodehydration under very mild conditions to give 2,3,6-trisubstituted pyridines with total regiocontrol.
- Bagley, Mark C.,Glover, Christian,Merritt, Eleanor A.,Xiong, Xin
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p. 811 - 814
(2007/10/03)
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- One-pot synthesis of pyridines or pyrimidines by tandem oxidation-heteroannulation of propargylic alcohols
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Pyridines and pyrimidines are prepared in a single step from propargylic alcohols by in situ oxidation with o-iodoxybenzoic acid or manganese dioxide and reaction with enamines or amidines, respectively, under either thermal or microwave-assisted conditions in a new one-pot tandem oxidation-heteroannulation procedure. The reaction of a β-ketoester, propargylic alcohol and ammonium acetate, with in situ oxidation, constitutes a highly facile three-component reaction for the synthesis of pyridines that accomplishes four distinct synthetic operations in one-pot, good yield and with total regiocontrol.
- Bagley, Mark C.,Hughes, David D.,Sabo, Halima M.,Taylor, Paul H.,Xiong, Xin
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p. 1443 - 1446
(2007/10/03)
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- A new one-step synthesis of pyridines under microwave-assisted conditions
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Tri- or tetrasubstituted pyridines are prepared by microwave irradiation of ethyl β-aminocrotonate and various alkynones in a single synthetic step and with total control of regiochemistry. This new one-pot Bohlmann-Rahtz procedure conducted at 170°C in a
- Bagley, Mark C,Lunn, Rebecca,Xiong, Xin
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p. 8331 - 8334
(2007/10/03)
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- Synthesis of tetrasubstituted pyridines by the acid-catalysed Bohlmann-Rahtz reaction
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New facile experimental procedures for the preparation of 2,3,4,6-tetrasubstituted pyridines in a single synthetic step have been developed. Thus, an enamino ester and alkynone react by Michael addition-cyclodehydration in a heterocyclisation process that is catalysed by acetic acid, Amberlyst 15 ion exchange resin, zinc(II) bromide or ytterbium(III) triflate. The new one-step Bronsted or Lewis acid-catalysed Bohlmann-Rahtz reaction is a simple, direct and highly expedient method for the synthesis of pyridines that proceeds at a lower reaction temperature and avoids the need to isolate reaction intermediates.
- Bagley, Mark C.,Brace, Christian,Dale, James W.,Ohnesorge, Maren,Phillips, Nathan G.,Xiong, Xin,Bower, Justin
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p. 1663 - 1671
(2007/10/03)
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- Synthesis of 6-Phenyl Substituted 2-Formylnicotinates
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A verastile synthesis of 2-formylnicotinates 6 (R' = Me) and 7 (R' = Et) is described. 6-Phenyl substituted 2-diethoxymethylnicotinates 14/15 are prepared first starting by cyclocondensation of 3-amino-4,4-diethoxybut-2-enoates 12/13 with Mannich base hydrochlorides 1 or β-aminovinyl ketones 16. Subsequent hydrolysis of the acetal function in 14/15 gives rise to the title compounds.
- Graef, Edgar,Troschuetz, Reinhard
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p. 1216 - 1222
(2007/10/03)
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- Carbon transfer reactions of functionalized oxazolidines and their open chain enamine tautomers to enamine nucleophiles. A facile synthesis of substituted pyridines and ring annulated derivatives
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Oxazolidines substituted at C-2 with -CH2-EW(-CO-, etc.) and capable of existing as ring-chain (enamine) tautomers react with cyclic, acyclic and heterocyclic enamine derivatives in a 1:1 stoi-chiometric manner to provide a versatile synthesis of substituted pyridines and their ring annulated derivatives.
- Singh, Kamaljit,Singh, Jasbir,Singh, Harjit
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p. 935 - 942
(2007/10/03)
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- Studies on Conjugated Nitriles. V. Reaction of 3-Benzoyl- and 3-Ethoxycarbonylacrylonitriles with Enamines
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The reactions of 3-benzoylacrylonitrile (1a) with 3-amino-5,5-dimethyl-2-cyclohexenone (2) and ethyl 3-aminocrotonate (4) gave the corresponding pyridine derivatives, 3 and 5, respectively. 3-Ethoxycarbonylacrylonitrile (1b) also reacted with ethyl 3-benzylaminocrotonate (6) and 1-ethoxycarbonylmethylene-1,2,3,4-tetrahydroisoquinoline (9) to give the pyrrolin-5-one derivatives, 7 and 10, respectively.Keywords - acrylonitrile derivative; enamine derivative; pyridine derivative; pyrrolin-5-one derivative; stannic chloride.
- Akiyama, Yasunobu,Abe, Junko,Takano, Tokuko,Kawasaki, Tomomi,Sakamoto, Masanori
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p. 2821 - 2824
(2007/10/02)
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