- CeCl3·7H2O-Catalyzed One-Pot Synthesis of Hantzsch 1,4-Dihydropyridines at Room Temperature
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An efficient synthesis of a series of 1,4-dihydropyridines was accomplished at room temperature by the reaction of aldehydes with ammonium acetate and ethyl acetoacetate catalyzed by CeCl3·7H2O.
- Sabitha, Gowravaram,Arundhathi,Sudhakar,Sastry,Yadav
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- Electrochemical-induced radical allylation via the fragmentation of alkyl 1,4-dihydropyridines
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Aldehydes are abundant chemical motifs presented in natural products and pharmaceuticals. As a radical precursor, its application is limited. Dihydropyridines (DHPs) can act as masked aldehydes, providing alkyl radicals under the activation of Lewis acid, heat, SET oxidant and light irradiation. Herein, we report the direct activation of 4-alkyl DHPs via single electron transfer at the anode. C–C bond homolysis at the C4-position of DHP generated the corresponding alkyl radical, which was captured subsequently by 2-phenyl and 2-ethoxy carbonyl allyl bromide. The following intramolecular elimination reaction afforded 20 different radical allylation products bearing various alkyl substituents with yields up to 92%.
- Chen, Xiaoping,Luo, Xiaosheng,Wang, Ping
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supporting information
(2022/02/02)
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- Visible-light-mediated alkylation of 4-alkyl-1,4-dihydropyridines with alkenyl sulfones
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Herein we report a mild, general protocol for visible-light-mediated alkylation of 4-alkyl-1,4-dihydropyridines with alkenyl sulfones. The protocol permits efficient functionalization of sulfones with a broad range of cyclic and acyclic secondary and tert
- Dong, Jianyang,Liu, Yuxiu,Wang, Qingmin,Yue, Fuyang
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supporting information
p. 8924 - 8928
(2021/11/04)
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- Enantioselective Alkylamination of Unactivated Alkenes under Copper Catalysis
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An enantioselective addition reaction of various alkyl groups to unactivated internal alkenes under Cu catalysis has been developed. The reaction uses amide-linked aminoquinoline as the directing group, 4-alkyl Hantzsch esters as the donor of alkyl radicals, and rarely used biaryl diphosphine oxide as a chiral ligand. β-lactams featuring two contiguous stereocenters at Cβ and the β substituent can be obtained in good yield with excellent enantioselectivity. Mechanistic studies indicate that a nucleophilic addition of the alkyl radical to CuII-coordinated alkene is the enantio-determining step.
- Bai, Zibo,Zhang, Heng,Wang, Hao,Yu, Hanrui,Chen, Gong,He, Gang
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supporting information
p. 1195 - 1202
(2021/02/05)
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- Visible-light-mediated minisci C-H alkylation of heteroarenes with 4-alkyl-1,4-dihydropyridines using O2as an oxidant
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Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation reactions of N-heteroarenes with 4-alkyl-1,4-dihydropyridines at room temperature with molecular oxygen as an oxidant. The protocol permits efficient functionalization of various N-heteroarenes with a broad range of cyclic and acyclic primary, secondary, and tertiary alkyl groups and is scalable to the gram level. This mild protocol uses an inexpensive, green oxidant and is suitable for late-stage C-H alkylation of complex nitrogen-containing molecules. We demonstrated its utility by preparing or functionalizing several pharmaceuticals and natural products.
- Dong, Jianyang,Liu, Yuxiu,Song, Hongjian,Wang, Qingmin,Xu, Wentao,Yue, Fuyang
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supporting information
p. 5599 - 5604
(2020/09/21)
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- Histidine-Specific Peptide Modification via Visible-Light-Promoted C-H Alkylation
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Histidine (His) carries a unique heteroaromatic imidazole side chain and plays irreplaceable functional roles in peptides and proteins. Existing strategies for site-selective histidine modification predominantly rely on the N-substitution reactions of the moderately nucleophilic imidazole group, which inherently suffers from the interferences from lysine and cysteine residues. Chemoselective modification of histidine remains one of the most difficult challenges in peptide chemistry. Herein, we report peptide modification via radical-mediated chemoselective C-H alkylation of histidine using C4-alkyl-1,4-dihydropyridine (DHP) reagents under visible-light-promoted conditions. The method exploits the electrophilic reactivity of the imidazole ring via a Minisci-type reaction pathway. This method exhibits an exceptionally broad scope for both peptides and DHP alkylation reagents. Its utility has been demonstrated in a series of important peptide drugs, complex natural products, and a small protein. Distinct from N-substitution reactions, the unsubstituted nitrogen groups of the modified imidazole ring are conserved in the C-H alkylated products.
- Chen, Xiaoping,Ye, Farong,Luo, Xiaosheng,Liu, Xueyi,Zhao, Jie,Wang, Siyao,Zhou, Qingqing,Chen, Gong,Wang, Ping
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supporting information
p. 18230 - 18237
(2019/11/14)
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- Intermolecular Radical Addition to Ketoacids Enabled by Boron Activation
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The intermolecular radical addition to the carbonyl group is difficult due to the facile fragmentation of the resulting alkoxyl radical. To date, the intermolecular radical addition to ketones, a valuable approach to construct quaternary carbon centers, remains a formidable synthetic challenge. Here, we report the first visible-light-induced intermolecular alkyl boronic acid addition to α-ketoacids enabled by the Lewis acid activation. The in situ boron complex formation is confirmed by various spectroscopic measurements and mechanistic probing experiments, which facilitates various alkyl boronic acid addition to the carbonyl group and prevents the cleavage of the newly formed C-C bond. Diversely substituted lactates can be synthesized from readily available alkyl boronic acids and ketoacids at room temperature merely under visible light irradiation, without any additional reagent. This boron activation approach can be extended to alkyl dihydropyridines as radical precursors with external boron reagents for primary, secondary, and tertiary alkyl radical additions. The pharmaceutically useful anticholinergic precursors are easily scaled up in multigrams under metal-free conditions in flow reactors.
- Xie, Shasha,Li, Defang,Huang, Hanchu,Zhang, Fuyuan,Chen, Yiyun
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supporting information
p. 16237 - 16242
(2019/10/14)
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- Photocatalytic Three-Component Umpolung Synthesis of 1,3-Diamines
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A visible-light-mediated photocatalytic umpolung synthesis of 1,3-diamines from in situ-generated imines and dehydroalanine derivatives is described. Pivoting on a key nucleophilic addition of photocatalytically generated α-amino radicals to electron-deficient alkenes, this three-component coupling reaction affords 1,3-diamines efficiently and diastereoselectively. The mild protocol tolerates a wide variety of functionalities including heterocycles, pinacol boronates, and aliphatic chains. Application to biologically relevant α-amino-γ-lactam synthesis and extension to 1,3-aminoalcohols is also demonstrated.
- Rossolini, Thomas,Leitch, Jamie A.,Grainger, Rachel,Dixon, Darren J.
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supporting information
p. 6794 - 6798
(2018/10/24)
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- Radical alkylation of: Para -quinone methides with 4-substituted Hantzsch esters/nitriles via organic photoredox catalysis
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A novel photocatalytic protocol is herein described for the preparation of functionalized phenols via radical alkylation of para-quinone methides under transition-metal-free conditions. The reaction is external oxidant free and performed at ambient temperature upon visible light irradiation, allowing the access to various desired products in satisfactory yields. The readily available 4-alkyl-1,4-dihydropyridines serve as the effective alkyl radical precursors.
- Wu, Qing-Yan,Min, Qing-Qiang,Ao, Gui-Zhen,Liu, Feng
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supporting information
p. 6391 - 6394
(2018/09/25)
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- Benzyltrimethylammoniumfluoride Hydrate: An Efficient Catalyst for One-Pot Synthesis of Hantzsch 1,4-Dihydropyridines and Their Aromatization
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An efficient, cost-effective and simple protocol has been developed for the synthesis of Hantzsch 1,4-dihydropyridines and their oxidation into pyridines using benzyltrimethylammonium fluoride hydrate as an excellent catalyst under solvent-free condition. All of the products synthesized by this method are characterized by various spectroscopic methods (IR, 1H NMR, 13C NMR, and DEPT).
- Khaskel, Anamika,Barman, Pranjit
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p. 114 - 120
(2016/04/01)
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- Synthesis of diethyl 4-substituted-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates as a new series of inhibitors against yeast α-glucosidase
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1,4-Dihydropyridine-3,5-dicarboxylate derivatives (1-25) were synthesized in high yields via Hantzsch reaction and evaluated for their α-glucosidase inhibitory activity. Compounds 1, 2, 6-8, 11, 13-15, and 23-25 showed a potent inhibitory activity against yeast α-glucosidase with IC50 values in the range of 35.0-273.7 μM, when compared with the standard drug acarbose (IC50 = 937 ± 1.60 μM). Their structures were characterized by different spectroscopic techniques. The kinetics, selectivity, and toxicity studies on these compounds were also carried out. The kinetic studies on most active compounds 14 and 25 determined their modes of inhibition and dissociation constants Ki. Compound 14 was found to be a non-competitive inhibitor with Ki = 25.0 ± 0.06, while compound 25 was identified as a competitive inhibitor with Ki = 66.0 ± 0.07 μM.
- Niaz, Huma,Kashtoh, Hamdy,Khan, Jalaluddin A. J.,Khan, Ajmal,Wahab, Atia-Tul,Alam, Muhammad Tanveer,Khan, Khalid Mohammed,Perveen, Shahnaz,Choudhary, M. Iqbal
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p. 199 - 209
(2015/04/14)
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- Urease: A highly biocompatible catalyst for switchable Biginelli reaction and synthesis of 1,4-dihydropyridines from the in situ formed ammonia
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Urease is a superior biocompatible catalyst for switching from the Biginelli reaction to urea-based synthesis of 1,4-dihydropyridines in water, where 100% switching occurs at 0.02 g/mL of enzyme. Hantzsch reaction with ammonium acetate (NH4OAc) is inefficiently catalyzed by urease (70%, 4 h), and heavy metal ions inhibit the urease-catalyzed reactions with urea or NH4OAc. Promotion of the urea-based Hantzsch reaction by urease and its inhibition with Hg2 + supports specificity of urease for in situ generation of ammonia, whereas the role of urease in further transformations is not so specific. The features of this enzymatic method are reusability, mild reaction conditions, biocompatibility, generality, and high yield of products.
- Tamaddon, Fatemeh,Ghazi, Somayeh
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- Alkyl transfer from C-C cleavage
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Hydrogenation was only the beginning: Hantzsch esters have now been used to transfer alkyl groups to imines under mild catalytic conditions to provide a variety of amines (see scheme). Benzyl, secondary alkyl, and tertiary alkyl groups containing ether, ester, and hydroxy functionalities were transferred successfully. The use of Hantzsch esters as alkylation reagents offers a practical and complementary alternative to organometallic processes. Copyright
- Li, Guangxun,Chen, Rong,Wu, Lei,Fu, Qingquan,Zhang, Xiaomei,Tang, Zhuo
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supporting information
p. 8432 - 8436
(2013/09/02)
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- Synthesis of some new 1,4-dihydropyridine derivatives through a facile one-pot Hantzsch condensation catalyzed by triethylamine
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A facile and efficient synthesis of new 1,4-dihydropyridine derivatives was reported via Hantzsch three-component condensation reaction of aldehydes or formylphenylboronic acids, ethyl acetoacetate, and ammonium acetate in the presence of a catalytic amount of triethylamine under solvent-free conditions. The method described here offers several advantages including high yields, short reaction times, and simple work-up procedure.
- Ghalem, Wassima,Boulcina, Raouf,Debache, Abdelmadjid
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experimental part
p. 733 - 737
(2012/05/20)
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- Thiamine hydrochloride-catalyzed one-pot synthesis of 1,4-dihydropyridine derivatives under solvent-free conditions
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An efficient one-pot synthesis of 1,4-dihydropyridines from an aldehyde, β-keto ester, and ammonium acetate or formamidine acetate using thiamine hydrochloride (VB1) as the catalyst under solvent-free conditions at ambient temperature is described. All types of aldehydes, including aromatic, aliphatic, and unsaturated aldehydes, give good yields. The catalyst can easily be recovered after completion of the reaction and reused without affecting its activity.
- Lei, Min,Ma, Lei,Hu, Lihong
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experimental part
p. 1969 - 1976
(2011/06/24)
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- Molybdenum- and tungsten-based coordination polymers as catalysts for an efficient and rapid synthesis of hexahydro-5-oxoquinoline-3-carboxylates and 1,4-Dihydropyridine-3,5-dicarboxylates
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Hexahydro-5-oxoquinoline-3-carboxylates and 1,4-dihydropyridine-3,5- dicarboxylates were synthesized efficiently and rapidly (2 min) in the presence of molybdenum- and tungsten-based coordination polymers [M(Bu 3Sn)2O4)]n (M=Mo or W) as catalysts (Schemes 1 and 2; Tables 2 and 3). The products were formed at room temperature in excellent yields (90-98%). The catalysts worked under heterogeneous conditions and were recyclable. The earlier reports for the application of these polymers to conduct organic synthesis are limited. The present method explores a new and useful application of these catalysts. Copyright
- Das, Biswanath,Srilatha, Malampati,Veeranjaneyulu, Boyapati,Kanth, Boddu Shashi
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experimental part
p. 885 - 891
(2011/06/24)
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- LiBr as an efficient catalyst for one-pot synthesis of Hantzsch 1,4-dihydropyridines under mild conditions
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A simple, inexpensive and efficient one-pot synthesis of 1,4-dihydropyridines has been accomplished via lithium bromide-catalyzed Hantzsch three-component condensation reaction of an aldehyde, αβ-ketoester and ammonium acetate in acetonitrile at room temperature in good to excellent yields. The present protocol is applicable to wide range of substrates including aliphatic, aromatic and heterocyclic aldehydes affording 1,4-dihydropyridines. A simple, inexpensive and efficient one-pot synthesis of 1,4-dihydropyridines has been accomplished via lithium bromide-catalyzed Hantzsch three-component condensation reaction of an aldehyde, αβ-ketoester and ammonium acetate in acetonitrile at room temperature in good to excellent yields. The present protocol is applicable to wide range of substrates including aliphatic, aromatic and heterocyclic aldehydes affording 1,4-dihydropyridines. Copyright
- Yadav,Patel,Srivastava,Watal,Yadav
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experimental part
p. 118 - 122
(2012/03/27)
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- Nano aluminium nitride as a solid source of ammonia for the preparation of hantzsch 1,4-dihydropyridines and bis-(1,4-dihydropyridines) in water via one pot multicomponent reaction
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Nano aluminium nitride in the presence of water acts as solid source of ammonia, which is used for the preparation of 1,4-dihydropyridines and bis-(1,4-dihydropyridines). An efficient and simple procedure for the one-pot synthesis of 1,4-dihydropyridine and bis-(1,4-dihydropyridine) derivatives was achieved by combination of methyl acetoacetate or ethyl acetoacetate with aldehydes or dialdehydes and aluminium nitride at 80 °C in water in high purity and good yields.
- Ghorbani-Choghamarani, Arash,Zolfigol, Mohammad Ali,Hajjami, Maryam,Goudarziafshar, Hamid,Nikoorazm, Mohsen,Yousefi, Somaieh,Tahmasbi, Bahman
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experimental part
p. 525 - 531
(2011/10/18)
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- Synthesis of 1,4-dihydropyridines using Ce(SO4)2-SiO2 as catalyst under solvent-free conditions
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A facile and efficient one-pot synthesis of 1,4-dihydropyridines from aldehyde, 1,3-dicarbonyl compounds and ammonium acetate in the presence of Ce(SO4)2-SiO2 at 80 °C under solvent-free conditions is described. Compared with the classical Hantzsch reaction, this novel method consistently has the advantages of excellent yields and short reaction time.
- Pei, Wen,Wang, Qin,Li, Xiaonian,Sun, Li
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experimental part
p. 483 - 486
(2010/10/02)
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- Synthesis of 3,4-dihydropyrimidin-2(1H)-ones and 1,4-dihydropyridines using ammonium carbonate in water
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Various known and new 3,4-dihydropyrimidin-2(1H)-ones and 1,4-dihydropyridines are prepared efficiently via Biginelli and Hantzsch reactions using ammonium carbonate in water. Competition between Biginelli and Hantzsch reactions is observed with pyridine carbaldehydes. Using this methodology, Hantzsch esters are synthesized in higher yields and purities than with other procedures without the use of a catalyst or an organic solvent.
- Tamaddon, Fatemeh,Razmi, Zahra,Jafari, Abbas Ali
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experimental part
p. 1187 - 1189
(2010/04/23)
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- Aromatization of 1,4-dihydropyridines using tetraethylammonium bromate as an oxidizing agent
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Quaternary ammonium bromate have been prepared from the corresponding bromide and used as a mild and efficient oxidizing agent for the aromatization of Hantzsch esters and related compounds to pyridine derivatives.
- Das, Pranab J.,Baruah, Akashi
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experimental part
p. 1568 - 1571
(2009/04/07)
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- Microwave-assisted oxidative aromatization of Hantzsch 1,4-dihydropyridines using manganese dioxide
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4-Aryl- and 4-alkyl-1,4-dihydropyridines, prepared by microwave-assisted Hantzsch reaction, are readily and efficiently aromatized in only one minute using commercial manganese dioxide in the absence of an inorganic support at 100 °C under microwave irradiation. This rapid procedure is more efficient than microwave-assisted aromatization using Pd/C, iodine or o-iodoxybenzoic acid (IBX) and gives the dehydrogenated or 4-dealkylated product in 91-100% yield (13 examples). Georg Thieme Verlag Stuttgart.
- Bagley, Mark C.,Lubinu, M. Caterina
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p. 1283 - 1288
(2007/10/03)
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- Unprecedented synthesis of hantzsch 1,4-dihydropyridines under biginelli reaction conditions
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Hantzsch 1,4-dihydropyridines are synthesized in high yields by a one-pot cyclocondensation of aldehyde, β-ketoester, and urea on the surface of silica gel under microwave irradiation in solvent-free conditions.
- Yadav,Subba Reddy,Reddy
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p. 425 - 430
(2007/10/03)
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- An efficient and fast procedure for the Hantzsch dihydropyridine synthesis under microwave conditions
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Abstract: A single-mode microwave cavity synthesizer with temperature and pressure control was used to accelerate the Hantzsch synthesis of 4-aryl and 4-alkyl-2,6-dimethyl-1,4-dihydro-3,5-pyridinedicarboxylates. In comparison with both conventional method
- ?hberg,Westman
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p. 1296 - 1298
(2007/10/03)
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- Ferric chloride hexahydrate: A convenient reagent for the oxidation of hantzsch 1,4-dihydropyridines
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A general and practical route for the moderate yield oxidative conversion of readily accessible 1,4-dihydropyridines (1,4-DHPs) to the corresponding pyridines was described using a relatively benign oxidant, i.e. ferric chloride hexahydrate (FeCl3·6H2O). The reaction was carried out under mild and convenient condition. However, oxidation of 4-isopropyl-1,4-DHP 1b with FeCl3·6H2O afforded the dealkylated pyridine 2a.
- Lu,Bai,Wang,Yang,Li
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p. 2625 - 2630
(2007/10/03)
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- BENTONITE K10 CLAY, AN EFFICIENT CATALYST FOR THE FORMATION OF NITROGEN DERIVATIVES
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Bentonite K10 clay has been used to catalyze the formation of enamino carbonyl derivatives, 2-methyl-1H-benzimidazoles, Hantzsch 1,4-dihydropyridines, Hantzsch pyridines, 2-substituted 1,3-diphenylimidazolidines, and tetrahydropyranylbenzazoles.
- Eynde, Jean Jacques Vanden,Mayence, Annie,Lor, Pascal,Haverbeke, Yves Van
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p. 387 - 392
(2007/10/02)
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- Novel syntheses of heterocycles with N-(1-haloalkyl)azinium halides. Part 2. Preparation of N-unsubstituted 1,4-dihydropyridines
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N-(1-Chloroalkyl)pyridinium chlorides, prepared from thionyl chloride, pyridine, and aldehydes, readily react with enaminocarbonyl derivatives to yield 1,4-dihydropyridines under mild and neutral conditions.
- Vanden Eynde,D'Orazio,Mayence,Maquestiau,Anders
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p. 1263 - 1268
(2007/10/02)
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