- Protodeboronation of (Hetero)Arylboronic Esters: Direct versus Prehydrolytic Pathways and Self-/Auto-Catalysis
-
The kinetics and mechanism of the base-catalyzed hydrolysis (ArB(OR)2→ ArB(OH)2) and protodeboronation (ArB(OR)2→ ArH) of a series of boronic esters, encompassing eight different polyols and 10 polyfluoroaryl and heteroaryl moieties, have been investigated by in situ and stopped-flow NMR spectroscopy (19F,1H, and11B), pH-rate dependence, isotope entrainment,2H KIEs, and KS-DFT computations. The study reveals the phenomenological stability of boronic esters under basic aqueous-organic conditions to be highly nuanced. In contrast to common assumption, esterification does not necessarily impart greater stability compared to the corresponding boronic acid. Moreover, hydrolysis of the ester to the boronic acid can be a dominant component of the overall protodeboronation process, augmented by self-, auto-, and oxidative (phenolic) catalysis when the pH is close to the pKaof the boronic acid/ester.
- Assante, Michele,Geogheghan, Katherine J.,Hayes, Hannah L. D.,Jin, Na,Leach, Andrew G.,Lloyd-Jones, Guy C.,Noonan, Gary,Tomasi, Simone,Wei, Ran
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supporting information
p. 14814 - 14826
(2021/09/13)
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- Cooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight
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An operationally simple and highly selective Au/Ag bimetallic-catalyzed cross-dehydrogenative biaryl coupling between pyrazoles and fluoroarenes has been developed. With this reaction, a wide range of biheteroaryl products can be obtained in moderate to good yields with excellent functional group compatibility. The exact role of silver salts, previously overlooked in most gold-catalyzed transformations, has been carefully investigated in this biaryl coupling. Insightful experimental and theoretical studies indicate that silver acetate is the actual catalyst for C-H activation of electron-poor arenes, rather than the previously reported gold(I)-catalyzed process. An unprecedented Au/Ag dual catalysis is proposed, in which silver(I) is responsible for the activation of electron-poor fluoroarenes via a concerted metalation-deprotonation pathway, and gold(III) is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that ArFnAu(III)-mediated C-H activation of pyrazoles is most likely the rate-limiting step.
- Li, Weipeng,Yuan, Dandan,Wang, Guoqiang,Zhao, Yue,Xie, Jin,Li, Shuhua,Zhu, Chengjian
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supporting information
p. 3187 - 3197
(2019/02/19)
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- Alkylation method for nitrogen-hydrogen containing compounds and application thereof
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The invention discloses an alkylation method for nitrogen-hydrogen containing compounds and an application thereof, belonging to the technical field of synthesis of organic compounds. The invention provides a series of methods for a nitrogen alkylation reaction of N-H containing heterocyclic compounds (II) with N,N-dimethylformamide dialkyl acetal as an alkyl source under the condition of no participation of metals, and a product with a hydrogen atom on a nitrogen atom substituted by R1 is obtained. The method provided by the invention has the advantages of highly-efficient reaction, high yield, simple treatment after the reaction, simple and convenient operation, mild reaction conditions, no participation of the metals, high tolerance of functional groups of a reaction substrate, wide range and easy preparation of the substrate, high reaction efficiency after amplification of the reaction, and applicability to large-scale industrial production.
- -
-
Paragraph 0059; 0060
(2018/10/04)
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- A practical and highly efficient reductive dehalogenation of aryl halides using heterogeneous Pd/AlO(OH) nanoparticles and sodium borohydride
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The reductive dehalogenation of aryl halides was performed by using commercially available aluminium oxy-hydroxide-supported palladium (Pd/AlO(OH)) nanoparticles of about 3?nm size (0.5?wt.?% Pd) with sodium borohydride. The dehalogenated products were obtained with absolute conversion in a mixture of H2O/MeOH (v/v=1/1) under ultrasonic conditions at room temperature. All aryl halides were successfully converted to halogen-free compounds within 1.5–4?h with yields of over 95%. The one-pot catalytic method is presented as a new process for the reductive dehalogenation of halogenated compounds. This method is quite simple, highly efficient and eco-friendly, and has an exceptional recovery rate.
- Kara, Belguzar Yasemin,Yazici, Melike,Kilbas, Benan,Goksu, Haydar
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p. 5898 - 5902
(2016/09/07)
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- Pyrazolium- versus imidazolium-based ionic liquids: Structure, dynamics and physicochemical properties
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Ionic liquids (ILs) composed of two different pyrazolium cations with dicyanamide and bis(trifluoromethanesulfonyl)imide anions have been synthesized and characterized by NMR, Kamlet-Taft solvatochromic parameters, conductivity and rheological measurements, as well as ab initio calculations. Density functional calculations for the two pyrazolium cations, 1-butyl-2- methylpyrazolium [bmpz] and 1-butyl-2,3,5-trimethylpyrazolium [bm 3pz], provide a full picture of their conformational states. Homo- and heteronuclear NOE show aggregation motives sensitive to steric hindrance and the anions' nature. Self-diffusion coefficients D for the anion and the cation have been measured by pulsed field gradient spin-echo NMR (PGSE-NMR). The ionic diffusivity is influenced by their chemical structure and steric hindrance, giving the order Dcation > Danion for all of the examined compounds. The measured ion diffusion coefficients, viscosities, and ionic conductivity follow the Vogel-Fulcher-Tammann (VFT) equation for the temperature dependencies, and the best-fit parameters have been determined. Solvatochromic parameters indicate an increased ion association upon going from bis(trifluoromethanesulfonyl)imide to dicyanamide-based pyrazolium salts, as well as specific hydrogen bond donor capability of H atoms on the pyrazolium ring. All of these physical properties are compared to those of an analogous series of imidazolium-based ILs.
- Chiappe, Cinzia,Sanzone, Angelo,Mendola, Daniele,Castiglione, Franca,Famulari, Antonino,Raos, Guido,Mele, Andrea
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p. 668 - 676
(2013/03/14)
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- Synthesis of biologically active seven-membered-ring heterocycles
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Seven-membered rings that contain one or more heteroatoms are interesting motifs for organic synthesis. In addition to their synthetic interest, they play an important role in industrial and pharmaceutical chemistry with generally increased central nervous system activity when flanked by aromatic rings. Herein we report a brief summary of some key methods of preparation for seven-membered-ring heterocycles and how they have been applied to the synthesis of commercially desirable products. We then detail new methods that we have developed for the synthesis of biologically active compounds containing this motif. Georg Thieme Verlag Stuttgart New York.
- Reekie, Tristan A.,Kavanagh, Madeline E.,Longworth, Mitchell,Kassiou, Michael
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p. 3211 - 3227
(2013/12/04)
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- Process development and large-scale synthesis of a c-Met kinase inhibitor
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A highly convergent synthesis of c-Met kinase inhibitor 1 has been demonstrated on a multikilogram scale using three key fragments: dihalotricyclic core 2, chiral sulfamide side chain 3, and pyrazole boronic ester 4. The chirality in sulfamide side chain 3 was installed using the cheap and readily available starting material (S)-epichlorohydrin. A total of 2.71 kg of 1 were isolated in seven steps (the longest linear sequence).
- Stewart, Gavin W.,Brands, Karel M. J.,Brewer, Sarah E.,Cowden, Cameron J.,Davies, Antony J.,Edwards, John S.,Gibson, Andrew W.,Hamilton, Simon E.,Katz, Jason D.,Keen, Stephen P.,Mullens, Peter R.,Scott, Jeremy P.,Wallace, Debra J.,Wise, Christopher S.
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scheme or table
p. 849 - 858
(2011/03/20)
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- An improved synthesis of 1-methyl-1H-pyrazole-4-boronic acid pinacol ester and its corresponding lithium hydroxy ate complex: application in Suzuki couplings
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An improved synthesis of 1-methyl-1H-pyrazole-4-boronic acid pinacol ester via isolation of the corresponding lithium hydroxy ate complex is described. The hydroxy ate complex is available in one pot from 4-bromo-1-methyl-1H-pyrazole and triisopropyl borate, and is isolated by filtration in high yield. Furthermore, the resulting lithium hydroxy ate complex has long-term bench stability and can be employed directly in Suzuki couplings without the need for added base.
- Mullens, Peter R.
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experimental part
p. 6783 - 6786
(2010/04/27)
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- PROCESSES FOR PRODUCING N-ALKYLPYRAZOLE
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Processes are provided for combining nonsubstituted hydrazine (N2H4), a strong acid, alcohol, and tetraalkoxypropane to produce N-alkylpyrazole.
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Page/Page column 4-5
(2009/12/05)
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- Two-stage sonogashira coupling method in the synthesis of auxin active acetylenes
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A sequential Sonogashira coupling of a protected acetylene precursor with aryl halides (5) followed by pyrazolyl iodides (14) allows efficient access to the unsymmetrical aryl-heteroarylacetylene (8). Subsequent regioselective lithiation exchange followed by dimethyl oxalate quench produced readily vicinal ketoesters (9) which show auxin effects in a wide variety of plant species.
- Wayne Craig,Eberle, Martin,Irminger, Bruno,Schueckenboehmer, Anegret,Laime, Yvette,Mueller, Patrick
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p. 1967 - 1974
(2008/09/16)
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- N-methylation of nitrogen-containing heterocycles with dimethyl carbonate
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Reactivity of dimethyl carbonate, the environmentally friendly reagent, as methylating agent for nitrogen-containing heterocyclic compounds has been studied. Reactions of imidazole, pyrazole, pyrrole, morpholine, and piperazine with dimethyl carbonate to afford N-methylated products were reported. The reactions were carried out with neither catalyst nor solvent at a temperature range of 110-170°C under atmospheric pressure. Copyright Taylor & Francis, Inc.
- Ouk, Samedy,Thiebaud, Sophie,Borredon, Elisabeth,Chabaud, Bernard
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p. 3021 - 3026
(2007/10/03)
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- Monomethylation of nitrogeneous heterocycles
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A process for the monomethylation of nitrogenous heterocycles having at least one nitrogen atom bonded to a hydrogen atom by reacting the nitrogenous heterocycle with dimethyl carbonate at a temperature of between 100° and 200° C. and a pressure of between 0.93×105 Pa and 1.07×105 Pa while methanol produced during the reaction is distilled off as it is formed.
- -
-
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- Synthesis of pinacol esters of 1-alkyl-1H-pyrazol-5-yl- and 1-alkyl-1H-pyrazol-4-ylboronic acids
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Starting from 1H-pyrazol, a wide number of 1-alkyl-1H-pyrazol-4-yl and 1-alkyl-1H-pyrazol-5-ylboronic acids and their pinacol esters were synthesized and characterized. The key step in the described methodology is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.
- Ivachtchenko, Alexandre V.,Kravchenko, Dmitry V.,Zheludeva, Valentina I.,Pershin, Dmitry G.
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p. 931 - 939
(2007/10/03)
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- Synthesis and reactions of the first allenyl azo compounds
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Several propargylhydrazines were prepared and then oxidized by manganese dioxide to generate short-lived 1,1-diazenes, which produced novel allenyl azo compounds (8) through [2,3] sigmatropic rearrangement. Isomerization of 8 or nucleophilic addition to the title compounds lead to hydrazones as well as pyrazole derivatives.
- Banert, Klaus,Hagedorn, Manfred,Schlott, Jana
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p. 360 - 361
(2007/10/03)
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- TRICYCLIC PYRIDINE N-OXIDES VASOPRESSIN AGONISTS
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The present invention provides compounds of general formula (I) as well as methods and pharmaceutical compositions utilizing these compounds for the inducement of temporary delay of urination or the treatment of disorders which may be remedied or alleviated by vasopressin agonist activity, including diabetes, insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders.
- -
-
-
- Tricyclic pyrido vasopressin agonists
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The present invention provides compounds of the general formula: wherein W is O or NH, optionally substituted, as well as methods and pharmaceutical compositions utilizing these compounds for the treatment of disorder which may be remedied or alleviated by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, or temporary delay of urination.
- -
-
-
- Tricyclic pyridine N-oxides vasopressin agonists
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The present invention provides compounds of the general formula: as well as methods and pharmaceutical compositions utilizing these compounds for the inducement of temporary delay of urination or the treatment of disorders which may be remedied or alleviated by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders.
- -
-
-
- Tricyclic vasopressin agonists
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The present invention provides compounds of the general formula: wherein W is O or NH, optionally substituted, as well as methods and pharmaceutical compositions utilizing these compounds for the treatment of disorder which may be remedied or alleviated by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, bleeding and coagulation disorders, or temporary delay of urination.
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-
-
- Enthalpies of formation of N-substituted pyrazoles and imidazoles
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Accurate experimental enthalpies of formation measured using static bomb combustion calorimetry, the "vacuum sublimation" drop calorimetry method, and the Knudsen-effusion method are reported for the first time for four azoles: 1-methylimidazole (1MeIMI), 1-methylpyrazole (1MePYR), 1-benzylimidazole (1BnIMI), and 1-benzylpyrazole (1BnPYR). These values and those corresponding to imidazole (1HIMI), pyrazole (1HPYR), 1-ethylimidazole (1EtIMI), 1-ethylpyrazole (1EtPYR), 1-phenylimidazole (1PhIMI), and 1-phenylpyrazole (1PhPYR) are compared with theoretical values using the G2(MP2) and the B3LYP/6-311*G(3df,2p)//6-31G(d) approaches. In general, there is a very good agreement between calculated and experimental values for the series of N-substituted imidazoles, while the agreement is less good for the series of the N-substituted pyrazoles. Experimentally, the gap between the enthalpies of formation of imidazoles and pyrazoles decreases significantly upon N-substitution, while the theoretical estimates indicate that this decrease is smaller.
- Mo?, Otilia,Ya?n?ez, Manuel,Roux, Mari?a Victoria,Jime?nez, Pilar,Da?valos, Juan Z.,Ribeiro da Silva, Manuel A. V.,Ribeiro da Silva, Maria Das Dores M. C.,Matos, M. Agostinha R.,Amaral, Luisa M. P. F.,Sa?nchez-Migallo?n, Ana,Cabildo, Pilar,Claramunt, Rosa,Elguero, Jose?,Liebman, Joel F.
-
p. 9336 - 9344
(2007/10/03)
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- Nucleophilic substitution at a four-coordinate sulfur atom. IV. Reactivity of anionic nitrogen-containing nucleopiles
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The second-order rate constants for reactions of anions derived from azoles, arenesulfonamides, and arenesulfonohydrazides with aryl toluenesulfonates and methyl iodide in 5% aqueous ethanol (μ 1.0) at 25°C were compared with corresponding rate constants for aliphatic and heterocyclic amines. The kinetic behavior of neutral and anionic nitrogen-containing bases in reactions involving acyl (4-nitrophenyl acetate and 4-nitrophenyl heptanoate) and toluenesulfonyl group transfer suggests that deviation from the Bronsted dependence is due to unfavorable solvation effects for nucleophiles with pKa ≥ 11.0 rather than to change in the transition state structure. In reactions with a soft substrate, methyl iodide, solvation effects scarcely play the determining role, and the reduced reactivity of the anionic nucleophiles relative to neutral species is most likely to result from structural differences in the transition states corresponding to methyl group transfer to neutral and anionic nitrogen-containing compounds. The α-effect with arenesulfonohydrazides was revealed for the first time. 1996 MAEe Cyrillic signΚ Hayκa/Interperiodica Publishing.
- Savelova,Karpichev,Simanenko,Prokop'eva,Lobachev,Belousova
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p. 530 - 539
(2007/10/03)
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- Synthesis of N-Alkylpyrazoles by Phase Transfer Catalysis without Solvent
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The alkylation of pyrazole is performed by phase transfer catalysis without solvent.High yields of N-alkylpyrazoles are obtained and the principal problems in the alkylation are suitably solved.
- Diez-Barra, E.,Hoz, A. de la,Sanchez-Migallon, A.,Tejeda, J.
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p. 2849 - 2853
(2007/10/02)
-
- Alkylation, Acylation and Silylation of Azoles
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Performing alkylation, acylation and silylation reactions in separate deprotonation and nucleophilic displacement steps allows for better control of reaction conditions and facilitates problem handling in these processes.In the alkylation of azoles the alkylating agents and solvents possess individual reaction capabilities which seem to be approximately additive.Monoalkylation occurs if the sum of the normalized reaction potentials is equal or larger than the pKa value of the azole.Dialkylation is avoided by keeping the sum of the normalized reaction potentials below the pKa value of the alkylazole.The applicability of these principles is demonstrated by the development of effective procedures for the methylation, benzylation, acetylation, methoxycarbonylation and trimethylsilylation of azoles.
- Begtrup, Mikael,Larsen, Peter
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p. 1050 - 1057
(2007/10/02)
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- Reissert Compound Formation with Fused Five-Membered Ring Heterocycles
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Reissert compounds have been prepared in high yield from benzothiazole by use of trimethylsilyl cyanide as source of cyanide in a single phase system.Analogues have been made from benzoxazole, indazole and 1-methylindazole but the method was unsuccessful with 1,2-benzisoxazole and pyrazole.Conjugate base alkylation followed by removal of the Reissert grouping provides a route to 2-alkylbenzothiazoles and -benzoxazoles, and 3-alkylated indazoles.Efficient access to pyridobenzothiazole and benzothiazoloisoquinoline derivatives results from appropriate intramolecular cyclisations.A crystal structure determination of 3-benzoyl-2,3-dihydro-2-benzothiazolecarbonitrile is reported.
- Uff, Barrie C.,Ho, Yee-Ping,Brown, David S.,Fisher, Ian,Popp, Frank D.,Kant, Joydeep
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p. 2652 - 2681
(2007/10/02)
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- FVP OF BIS- AND TRIS-(PYRAZOL-1-YL)METHANE. A RADICAL REACTION
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Flash vacuum pyrolysis of bis- and tris-(pyrazol-1-yl) methane was carried out.Alpha, gamma and radical eliminations were considered.The products actually formed correspond to a radical reaction.In the case of bis-(pyrazol-1-yl)methane, working at higher temperatures, pyrimidine was obtained.This compound is formed by rearrangement of a PzCH2. radical.
- Perez, Jorge D.,Yranzo, Gloria I.,Ferraris, Marisa A.,Claramunt, Rosa M.,Lopez, Concepcion,Elguero, Jose
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p. 6429 - 6434
(2007/10/02)
-
- Preparation of pyrazoles
-
A process for the preparation of pyrazoles by reacting a pyrazoline with sulfur or selenium in a solvent.
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- Regioselective Halo- and Carbodesilylation of (Trimethylsilyl)-1-methylpyrazoles
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The isomeric 3-, 4-, and 5-(trimethylsilyl)- as well as the 3,4-, 3,5-, and 4,5-bis(trimethylsilyl)-1-methylpyrazoles (2, 7, 3, 5, 9, and 10, respectively) are obtained by methylation of the corresponding (trimethylsilyl)-1H-pyrazoles or by silylation of Grignard or lithio derivatives of appropriate 1-methylpyrazoles with chlorotrimethylsilane. 5 and 10 are halodesilylated regioselectively by Br2 or ICl in the 4-position, yielding 13 and 15.With addditional bromine, these monobromo compounds suffer exclusively bromodesilylation to give 3,4- and 4,5-dibromo-1-methylpyrazole (14 and 16, respectively).These findings are in accord with the electrophilic substitution reactivity indices for 1-methylpyrazole (8) and with ipso-directing influence of the Me3Si group.The reaction of 5 with I2, unexpectedly, attacks preferentially at the 3-position.Regioselective carbodesilylation in the 5-position is observed in the fluoride-catalyzed reactions of 3, 9, and 10 with carbon electrophiles.The high regiospecificity of this reaction is rationalized in terms of carbanion stabilization at the individual pyrazole positions.
- Effenberger, Franz,Krebs, Andreas
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p. 4687 - 4695
(2007/10/02)
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- AMINATION OF ISOMERIC BROMO-1-METHYLNITROPYRAZOLES
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A method was developed for the synthesis of 5-bromo-1-methyl-4-nitropyrazole from 1-methylpyrazole.In the reaction with 25percent aqueous ammonia at 180-190 deg C, 5-bromo-1-methyl-4-nitropyrazole is readily converted to 5-amino-1-methyl-4-nitropyrazole; the production of 4-amino-1-methyl-5-nitropyrazole from 4-bromo-1-methyl-5-nitropyrazole requires the presence of a copper catalyst; under the same conditions in the amination of 4-bromo-1-methyl-3-nitropyrazole, 4-amino-1-methyl-3-nitro- and 1-methyl-3-nitropyrazoles are formed in a 2 : 3 ratio.
- Perevalov, V. P.,Baryshnenkova, L. I.,Andreeva, M. A.,Manaev, Yu. A.,Denisova, I. A.,et al.
-
p. 1322 - 1326
(2007/10/02)
-
- Phase-Transfer Alkylation of Heterocycles in the Presence of 18-Crown-6 and Potassium tert-Butoxide
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It has been found that the N-alkylation of heterocyclic compounds bearing an acidic hydrogen atom attached to nitrogen can be accomplished in diethyl ether via a phase-transfer process in which 18-crown-6 is employed as the catalyst and potassium tert-butoxide is employed as the base.In this manner, pyrrole (1), indole (2), pyrazole (3), imidazole (4), benzimidazole (5), benzotriazole (6), carbazole (7), and methyl indole-3-acetate (8) can be successfully alkylated.The procedure is convenient and mild and generally gives rise to exclusive N-alkylation.
- Guida, Wayne C.,Mathre, David J.
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p. 3172 - 3176
(2007/10/02)
-
