- Cu(OTf)2-Mediated Cross-Coupling of Nitriles and N-Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products**
-
Metal-catalyzed C–N cross-coupling generally forms C?N bonds by reductive elimination from metal complexes bearing covalent C- and N-ligands. We have identified a Cu-mediated C–N cross-coupling that uses a dative N-ligand in the bond-forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a CuII complex bearing neutral N-ligands, such as nitriles or N-heterocycles. Subsequent generation of a putative CuIII complex enables the oxidative C–N coupling to take place, delivering nitrilium intermediates and pyridinium products. The reaction is general for a range of N(sp) and N(sp2) precursors and can be applied to drug synthesis and late-stage N-arylation, and the limitations in the methodology are mechanistically evidenced.
- Bell, Nicola L.,Xu, Chao,Fyfe, James W. B.,Vantourout, Julien C.,Brals, Jeremy,Chabbra, Sonia,Bode, Bela E.,Cordes, David B.,Slawin, Alexandra M. Z.,McGuire, Thomas M.,Watson, Allan J. B.
-
supporting information
p. 7935 - 7940
(2021/03/03)
-
- A novel construction of acetamides from rhodium-catalyzed aminocarbonylation of DMC with nitro compounds
-
Dimethyl carbonate (DMC), an environment-friendly compound prepared from CO2, shows diverse reactivities. In this communication, an efficient procedure using DMC as both a C1 building block and solvent in the aminocarbonylation reaction with nitro compounds has been developed. W(CO)6acts both a CO source and a reductant here.
- Bao, Zhi-Peng,Miao, Ren-Guan,Qi, Xinxin,Wu, Xiao-Feng
-
supporting information
p. 1955 - 1958
(2021/03/02)
-
- Discovery of new phenyl sulfonyl-pyrimidine carboxylate derivatives as the potential multi-target drugs with effective anti-Alzheimer's action: Design, synthesis, crystal structure and in-vitro biological evaluation
-
Alzheimer's disease (AD) is multifactorial, progressive neurodegeneration with impaired behavioural and cognitive functions. The multitarget-directed ligand (MTDL) strategies are promising paradigm in drug development, potentially leading to new possible therapy options for complex AD. Herein, a series of novel MTDLs phenylsulfonyl-pyrimidine carboxylate (BS-1 to BS-24) derivatives were designed and synthesized for AD treatment. All the synthesized compounds were validated by 1HNMR, 13CNMR, HRMS, and BS-19 were structurally validated by X-Ray single diffraction analysis. To evaluate the plausible binding affinity of designed compounds, molecular docking study was performed, and the result revealed their significant interaction with active sites of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The synthesized compounds displayed moderate to excellent in vitro enzyme inhibitory activity against AChE and BuChE at nanomolar (nM) concentration. Among 24 compounds (BS-1 to BS-24), the optimal compounds (BS-10 and BS-22) displayed potential inhibition against AChE; IC50 = 47.33 ± 0.02 nM and 51.36 ± 0.04 nM and moderate inhibition against BuChE; IC50 = 159.43 ± 0.72 nM and 153.3 ± 0.74 nM respectively. In the enzyme kinetics study, the compound BS-10 displayed non-competitive inhibition of AChE with Ki = 8 nM. Respective compounds BS-10 and BS-22 inhibited AChE-induced Aβ1-42 aggregation in thioflavin T-assay at 10 μM and 20 μM, but BS-10 at 10 μM and 20 μM concentrations are found more potent than BS-22. In addition, the aggregation properties were determined by the dynamic light scattering (DLS) and was found that BS-10 and BS-22 could significantly inhibit self-induced as well as AChE-induced Aβ1-42 aggregation. The effect of compounds (BS-10 and BS-22) on the viability of MC65 neuroblastoma cells and their capability to cross the blood-brain barrier (BBB) in PAMPA-BBB were further studied. Further, in silico approach was applied to analyze physicochemical and pharmacokinetics properties of the designed compounds via the SwissADME and PreADMET server. Hence, the novel phenylsulfonyl-pyrimidine carboxylate derivatives can act as promising leads in the development of AChE inhibitors and Aβ disaggregator for the treatment of AD.
- Manzoor, Shoaib,Prajapati, Santosh Kumar,Majumdar, Shreyasi,Raza, Kausar,Gabr, Moustafa T.,Kumar, Shivani,Pal, Kavita,Rashid, Haroon,Kumar, Suresh,Krishnamurthy, Sairam,Hoda, Nasimul
-
-
- Manganese(I) Catalyzed α-Alkenylation of Amides Using Alcohols with Liberation of Hydrogen and Water
-
Herein, unprecedented manganese-catalyzed direct α-alkenylation of amides using alcohols is reported. Aryl amides are reacted with diverse primary alcohols, which provided the α,β-unsaturated amides in moderate to good yields with excellent selectivity. Mechanistic studies indicate that Mn(I) catalyst oxidizes the alcohols to their corresponding aldehydes and also plays an important role in efficient C═C bond formation through aldol condensation. This selective olefination is facilitated by metal-ligand cooperation by the aromatization-dearomatization process operating in the catalytic system. Biorenewable alcohols are used as alkenylation reagents for the challenging α-alkenylation of amides with the highly abundant base metal manganese as a catalyst, which results in water and dihydrogen as the only byproduct, making this catalytic transformation attractive, sustainable, and environmentally benign.
- Pandia, Biplab Keshari,Gunanathan, Chidambaram
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p. 9994 - 10005
(2021/07/31)
-
- Efficient nitriding reagent and application thereof
-
The invention discloses an efficient nitriding reagent and application thereof, wherein the nitriding reagent comprises nitrogen oxide, an active agent, a reducing agent and an organic solvent. By applying the nitriding reagent, nitrogen-containing compounds such as amide, nitrile and the like can be produced, and the method is simple in condition, low in waste discharge amount and simple in reaction equipment.
- -
-
Paragraph 0152-0154
(2021/03/31)
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- A one pot protocol to convert nitro-arenes into: N-aryl amides
-
A two-step one pot, experimentally simple protocol, based on readily available and inexpensive reagents allowed the conversion of nitro-arenes directly to N-aryl amides. A metal-free reduction of the nitro group, mediated by trichlorosilane, followed by the addition of an anhydride afforded the corresponding N-aryl carboxyamide, that was isolated after a simple aqueous work up in good-excellent yields. When the methodology was applied to the reaction with γ-butyrolactone, the desired N-aryl butanamide derivative was obtained, featuring a chlorine atom at the γ-position, a functionalized handle that can be used for further synthetic manipulation of the reaction product. Such an intermediate has already been employed as a key advanced precursor of pharmaceutically active compounds.
- Massolo, Elisabetta,Pirola, Margherita,Puglisi, Alessandra,Rossi, Sergio,Benaglia, Maurizio
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p. 4040 - 4044
(2020/02/04)
-
- Overcoming imatinib resistance in chronic myelogenous leukemia cells using non-cytotoxic cell death modulators
-
Recent studies examined the possibility to overcome imatinib resistance in chronic myeloid leukemia (CML) patients by combination therapy with peroxisome proliferator-activated receptor gamma (PPARγ) ligands. Pioglitazone, a full PPARγ agonist, improved the survival of patients by the gradual elimination of the residual CML stem cell pool. To evaluate the importance of the pharmacological profile of PPARγ agonists on the ability to circumvent resistance, the partial PPARγ agonist 4‘-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1’-biphenyl]-2-carboxylic acid, derived from telmisartan, and other related derivatives were investigated. The 4-substituted benzimidazole derivatives bearing a [1,1′-biphenyl]-2-carboxamide moiety sensitized K562-resistant cells to imatinib treatment. Especially the derivatives 18a-f, which did not activate PPARγ to more than 40% at 10 μM, retrieved the cytotoxicity of imatinib in these cells. The cell death modulating properties were higher than that of pioglitazone. It is of interest to note that all novel compounds were not cytotoxic neither on non-resistant nor on resistant cells. They exerted antitumor potency only in combination with imatinib.
- Schoepf, Anna M.,Salcher, Stefan,Obexer, Petra,Gust, Ronald
-
supporting information
(2019/10/22)
-
- Nitromethane as a nitrogen donor in Schmidt-type formation of amides and nitriles
-
The Schmidt reaction has been an efficient and widely used synthetic approach to amides and nitriles since its discovery in 1923. However, its application often entails the use of volatile, potentially explosive, and highly toxic azide reagents. Here, we report a sequence whereby triflic anhydride and formic and acetic acids activate the bulk chemical nitromethane to serve as a nitrogen donor in place of azides in Schmidt-like reactions. This protocol further expands the substrate scope to alkynes and simple alkyl benzenes for the preparation of amides and nitriles.
- Jiao, Ning,Liu, Jianzhong,Qiu, Xu,Song, Song,Wei, Jialiang,Wen, Xiaojin,Zhang, Cheng,Zhang, Ziyao
-
supporting information
p. 281 - 285
(2020/01/28)
-
- Synthesis of diverse libraries of carboxamides via chemoselective N-acylation of amines by carboxylic acids employing Br?nsted acidic IL [BMIM(SO3H)][OTf]
-
Chemoselective N-acylation of amines with carboxylic acids as acyl electrophiles and Br?nsted acidic IL [BMIM(SO3H)][OTf] as promoter is reported under both thermal and microwave irradiation to produce libraries of carboxamides in good to excellent yields after a simple workup. The protocol is compatible with structurally diverse 1° and 2° amines and works in the presence of sensitive functional groups such as thiols and phenols. The potential for recycling and reuse of the IL is also demonstrated.
- Savanur, Hemantkumar M.,Malunavar, Shruti S.,Prabhala, Pavankumar,Sutar, Suraj M.,Kalkhambkar, Rajesh G.,Laali, Kenneth K.
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supporting information
(2019/09/30)
-
- Regioselective nitration of anilines with Fe(NO3)3·9H2O as a promoter and a nitro source
-
An efficient Fe(NO3)3·9H2O promoted ortho-nitration reaction of aniline derivatives has been developed. This reaction may go through a nitrogen dioxide radical (NO2) intermediate, which is generated by the thermal decomposition of iron(iii) nitrate. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the broad substrate scope and applications.
- Gao, Yang,Mao, Yuanyou,Zhang, Biwei,Zhan, Yingying,Huo, Yanping
-
supporting information
p. 3881 - 3884
(2018/06/08)
-
- Combining Eosin y with Selectfluor: A Regioselective Brominating System for Para-Bromination of Aniline Derivatives
-
A mild, metal-free, and absolutely para-selective bromination of aniline derivatives has been developed in excellent yields, wherein the organic dye Eosin Y is employed as the bromine source in company with Selectfluor. Neither air nor moisture sensitive, this facile reaction proceeds smoothly at room temperature and completes within a short time. Mechanistic studies indicate a radical pathway; therefore, the existence of an in situ generated brominating reagent, "Selectbrom", is postulated, which may reasonably account for the unique regioselectivity for the para-bromination of N-acyl- as well as N-sulfonylanilines.
- Huang, Binbin,Zhao, Yating,Yang, Chao,Gao, Yuan,Xia, Wujiong
-
supporting information
p. 3799 - 3802
(2017/07/26)
-
- Amide-assisted radical strategy: Metal-free direct fluorination of arenes in aqueous media
-
A metal- and initiator-free direct fluorination of arenes with the assistance of an amide group is developed. This reaction proceeded under simple aqueous conditions with good functional group tolerance and ortho-para selectivity, and is highly practical because it could be readily scaled up to a multigram-scale. At this stage, an exclusive mechanism could not be proposed, and several possibilities have been discussed. The possibility of the amide-assisted radical chain mechanism has been supported by experimental and computational investigations as well as a seminal work.
- Liang, Deqiang,Li, Yanni,Gao, Shulin,Li, Renlun,Li, Xiangguang,Wang, Baoling,Yang, Hai
-
supporting information
p. 3344 - 3349
(2017/07/28)
-
- Palladium-Catalyzed, ortho-Selective C-H Halogenation of Benzyl Nitriles, Aryl Weinreb Amides, and Anilides
-
A palladium-catalyzed, ortho-selective C-H halogenation methodology is reported herein. The highlight of the work is the highly selective C(sp2)-H functionalization of benzyl nitriles in the presence of activated C(sp3)-H bond, which results in good yields of the halogenated products with excellent regioselectivity. Along with benzyl nitriles, aryl Weinreb amides and anilides have been evaluated for the transformation using aprotic conditions. Mechanistic studies yield interesting aspects with respect to the pathway of the reaction and the directing group abilities.
- Das, Riki,Kapur, Manmohan
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p. 1114 - 1126
(2018/06/18)
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- AIBN-promoted amidation of anilines with 1, 3-diketones via oxidative cleavage of C–C bond under aerobic conditions
-
N-Acylation of anilines with 1, 3-diketones promoted by AIBN (2-2′-azoisobutyronitrile) under metal-free and peroxide-free conditions in the presence of molecular oxygen as oxidant has been described. This protocol proceeds by the oxidative cleavage of C–C bond with simultaneous intermolecular C–N bond formation under mild conditions.
- Rao, Sadu Nageswara,Mohan, Darapaneni Chandra,Adimurthy, Subbarayappa
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p. 4889 - 4894
(2016/07/18)
-
- Cleavage of C-N bonds in guanidine derivatives and its relevance to efficient C-N bonds formation
-
Efficient nonenzymatic decomposition of guanidine derivatives with high structural and functional diversity into anilide products is achieved in the presence of PdII/Cu(II) carboxylates/CO, relying on a dual C-N bonds cleavage strategy. In this decomposition process, the cooperative action of PdII species, Cu(II) carboxylates, and CO provides not only the N-acylating agents but also an initiator to trigger this C-N bonds cleavage sequence. The current results indicate that PdII/Cu(II) carboxylates/CO system provides a convenient and practical method for highly selective cleavage of unreactive C-N single bonds.
- Chang, Denghu,Zhu, Dan,Zou, Peng,Shi, Lei
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p. 1684 - 1693
(2015/03/30)
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- Pd-Catalyzed C-H activation/oxidative cyclization of acetanilide with norbornene: Concise access to functionalized indolines
-
An efficient Pd-catalyzed oxidative cyclization reaction for the synthesis of functionalized indolines by direct C-H activation of acetanilide has been developed. The norbornylpalladium species formed via direct ortho C-H activation of acetanilides is supposed to be a key intermediate in this transformation. This journal is the Partner Organisations 2014.
- Gao, Yang,Huang, Yubing,Wu, Wanqing,Huang, Kefan,Jiang, Huanfeng
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supporting information
p. 8370 - 8373
(2014/07/22)
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- Quantitative insights into energy contributions of intermolecular interactions in fluorine and trifluoromethyl substituted isomeric N-phenylacetamides and N-methylbenzamides
-
The presence of the C-F bond in organic molecules, particularly in the context of generating different intermolecular interactions of the type C-F...F-C, C-H...F and C-F...π is of extreme significance in the realm of structural chemistry. These interactions generate different packing motifs in the formation of the crystal. It is of interest to evaluate the energetic contributions of such weak interactions to evaluate their important role in crystal packing. In this respect, a library of twelve compounds containing a strong donor and acceptor, along with the presence of a C-F bond in different electronic environments (fluorine atom connected to C(sp2) and C(sp3) carbon atom) have been synthesized and characterized using single crystal X-ray diffraction studies at low temperature. In addition, the non-fluorinated counterpart has also been synthesized. These crystal structures have been analyzed to understand the contribution of weak interactions involving organic fluorine in the crystal packing. Furthermore, the stabilizing-destabilizing roles of such interactions in terms of favourable energetics have been quantified with inputs from calculations performed using PIXEL. It is observed that most of the interactions involving fluorine are of a dispersive character, and in some cases the interaction is also coulombic in origin. These results have been compared with ab initio quantum-chemical calculations (DFT-D3/B-97D level) performed using TURBOMOLE. In addition, the lattice energies of all the compounds have been evaluated, and the total contribution partitioned into the corresponding coulombic, polarization, dispersion and exchange contributions using the CLP module. The results correlate well with thermochemical data experimentally determined for these compounds.
- Panini, Piyush,Chopra, Deepak
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p. 3711 - 3733
(2013/07/26)
-
- Oxidative para- Triflation of acetanilides
-
Direct triflation of acetanilide derivatives with silver triflate has been accomplished under mild iodine(III)-mediated oxidative conditions. The reaction shows excellent regioselectivity for the para position and tolerates a range of ortho and meta substituents on the aromatic ring. This method is also compatible with the preparation of arylnonaflates in synthetically useful yields.
- Pialat, Amelie,Liegault, Benoit,Taillefer, Marc
-
supporting information
p. 1764 - 1767
(2013/06/26)
-
- Efficient amide formation from arylamines and esters promoted by AlCl 3/Et3N: An experimental and computational investigation
-
Efficient and selective preparation of amides from arylamines and esters has been achieved with an AlCl3/Et3N pair under mild conditions. A large number of arylamines were successfully acylated to the corresponding amides in high yields and short reaction times. For instance, a 94% yield of p-bromoacetanilide was obtained from p-bromoaniline and ethyl acetate in 10 min at room temperature. In addition, a computational study on the N-acylation of amines was performed using density functional theory. It was found that the energy barrier for N-acylation of aniline is 10 kcal/mol higher than that of methylamine. In the presence of AlCl3, the activation energy for the N-acylation of aniline was reduced by 27.7 kcal/mol with the endothermic process becoming exothermic. Springer Science+Business Media B.V. 2012.
- Tong, Xinli,Ren, Zhangshun,Que, Xiaolong,Yang, Qiwu,Zhang, Wenqin
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p. 1961 - 1968
(2013/02/22)
-
- Antiviral Compounds
-
Novel compounds, methods, and compositions for treating various viral infections are described. In some embodiments the novel compounds of the invention are 3-oxo-phenothiazine derivatives; more specific embodiments include 3-oxo-phenothiazine derivatives having substituents at the 1-, 7-, and 9-positions of the phenothiazine parent ring. In other embodiments, the invention provides compositions and methods for treating viral infections, especially HIV.
- -
-
Page/Page column 13
(2012/09/25)
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- Antiviral Compounds
-
Compounds and methods for preventing and treating viral infections are provided. In some embodiments, novel compounds broad-spectrum antiviral activity are provided. In more specific embodiments, the compounds and methods are effective against viruses such as Venezuelan Equine Encephalitis, West Nile Virus, and Hepatitis C.
- -
-
Page/Page column 20
(2012/11/07)
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- Reductive dehalogenation of aryl bromides and chlorides and their use as aryl blocking groups
-
Bromo and chloro substituents serve as excellent blocking groups on aromatic rings. When a halo substituent is para to an ortho,para-directing group, the ortho positions can be easily functionalized, and the halo group can be subsequently removed by catalytic hydrogenation under neutral conditions. As expected, bromides are reduced more quickly than chlorides and the reaction requires the use of less catalyst. Bromides can be selectively reduced in the presence of nitro, chloro, cyano, keto, or carboxylic acid groups. Georg Thieme Verlag Stuttgart.
- Ramanathan, Ahalya,Jimenez, Leslie S.
-
experimental part
p. 217 - 220
(2010/04/05)
-
- SYNTHETIC METHODS AND COMPOSITIONS
-
The invention provides synthetic methods that utilize bromo or chloro substituents as blocking groups during the functionalization of aromatic rings, as well as compounds that are prepared from such methods.
- -
-
Page/Page column 4; 5
(2011/01/11)
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- QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
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The present invention relates to novel quinolones of Formula I that inhibit inducible NOS synthase together with methods of synthesizing and using the compounds including methods for inhibiting or modulating nitric oxide synthesis and/or lowering nitric oxide levels in a patient by administering the compounds for the treatment of disease.
- -
-
Page/Page column 80
(2008/12/06)
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- Facile synthesis and herbicidal activities of new isoxazole derivatives via 1,3-dipolar cycloaddition reaction
-
A series of cycloadducts via 1,3-dipolar cycloaddition reactions of generated nitrile oxides with N-(4-chloro-2-fluorophenyl) maleimides were described. The reaction of N-(4-chloro-2-fluorophenyl) maleimides with nitrile oxides gave 3,5-diaryl-3a,6a-dihydropyrroio[3,4-d]isoxazole-4,6-diones through syn-addition pattern. The title compounds were characterized by 1H NMR, IR, MS, and elemental analysis or HRMS. The single crystal structure of 6i was determined by X-ray diffraction. The herbicidal activities of the title compounds were evaluated. Some of them exhibited certain herbicidal activities against barnyardgrass and rape.
- Zhang, Chuan-Yu,Wang, Bao-Lei,Liu, Xing-Hai,Li, Yong-Hong,Wang, Su-Hua,Li, Zheng-Ming
-
experimental part
p. 397 - 404
(2010/03/24)
-
- Synthesis and antimicrobial evaluation of guanylsulfonamides
-
A series of guanylsulfonamides, 2-amino-9-[2-substituted-4-(4-substituted piperidin-1-sulfonyl)phenyl]-1,9-dihydropurin-6-ones, was synthesized by adopting reductive aminoformylation of 2-amino-5-nitro-6-[4-(piperidin-1-sulfonyl)phenylamino]-3H-pyrimidin- 4-one and subsequent intramolecular ring condensation as key steps. All the guanylsulfonamides were assayed for their in vitro antibacterial activities against Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, and Streptococcus faecalis, and their antifungal activities against Aspergillus flavus, Aspergillus niger, and Candida albicans. Of the guanylsulfonamides, 13e and 13f displayed better antibacterial activities than that of Norfloxacin against the bacterial strains S. aureus and S. faecalis except 13f against S. faecalis, which exhibited the activity similar to that of Norfloxacin. Against the fungal strains A. flavus and A. niger, 13g and 13h showed similar activities to that of Griseoflavin-16 except 13h against A. niger, which displayed a profound drop in the activity compared to that of Griseoflavin-16. The remarkable inhibition of the growth of the bacterial and fungal strains makes these substances promising microbial agents.
- Patel, Pratik R.,Ramalingan, Chennan,Park, Yong-Tae
-
p. 6610 - 6614
(2008/09/18)
-
- Chemoselective acylation of amines in aqueous media
-
Amines are efficiently acylated by both cyclic and acyclic anhydrides by dissolving them in an aqueous medium with the help of a surfactant, sodium dodecyl sulfate (SDS). Cyclic and acyclic anhydrides react with equal ease with an amine, and amines with various stereo-electronic factors react at the same rates with an anhydride. Chemoselective acylation of amines in the presence of phenols and thiols and of thiols in the presence of phenols has been achieved. No acidic or basic reagents are used during the reaction. No Chromatographic separation is required for isolation of the acylated products. Reactions in a neutral aqueous medium, easy isolation of products, and innocuous by-products make the present method a green chemical process. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Naik, Sarala,Bhattacharjya, Gitalee,Talukdar, Bandana,Patel, Bhisma K.
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p. 1254 - 1260
(2007/10/03)
-
- Indium-mediated one-pot reductive conversion of nitroarenes to N-arylacetamides
-
N-Arylacetamides were prepared in excellent yields from nitroarenes in the presence of acetic anhydride, acetic acid and indium by a one-pot procedure.
- Kim, Byeong Hyo,Han, Rongbi,Piao, Fengyu,Jun, Young Moo,Baik, Woonphil,Lee, Byung Min
-
-
- Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives
-
Two series of halogenated sulfonamides have been prepared. The first consists of mono/ dihalogenated sulfanilamides, whereas the second one consists of the mono/dihalogenated aminobenzolamides, incorporating equal or different halogens (F, Cl, Br, and I). These sulfonamides have been synthesized from the corresponding anilines by acetylation (protection of the amino group), chlorosulfonylation, followed either by amidation, or reaction with 5-amino1,3,4-thiadiazole-2-sulfonamide (and eventually deacetylation). All these compounds, together with the six clinically used sulfonamide inhibitors (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, and brinzolamide) were investigated as inhibitors of the transmembrane, tumor-associated isozyme carbonic anhydrase (CA) IX. Inhibition data against the classical, physiologically relevant isozymes I, II, and IV were also obtained. CA IX shows an inhibition profile which is generally completely different from those of isozymes I, II, and IV, with potent inhibitors (inhibition constants in the range of 12-40 nM) among both simple aromatic (such as 3-fluoro-5-chloro-4-aminobenzenesulfonamide) as well as heterocyclic compounds (such as acetazolamide, methazolamide, 5-amino-1,3,4-thiadiazole-2-sulfonamide, aminobenzolamide, and dihalogenated aminobenzolamides). This first detailed CA IX inhibition study revealed many interesting leads, suggesting the possibility to design even more potent and eventually CA IX-selective inhibitors, with putative applications as antitumor agents.
- Ilies, Marc A.,Vullo, Daniela,Pastorek, Jaromir,Scozzafava, Andrea,Ilies, Monica,Caproiu, Miron T.,Pastorekova, Silvia,Supuran, Claudiu T.
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p. 2187 - 2196
(2007/10/03)
-
- 1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate): An electrophilic fluorinating agent
-
1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), NFTh, is a electrophilic fluorinating that can be used to fluorinate aromatic rings, olefins, dienol acetates and enol ethers. When NFTh is reacted with an active methylene compound in the presence of ZnCl2, the corresponding mono- or di-fluoro derivative can be isolated.
- Poss, Andrew J.,Shia, George A.
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p. 2673 - 2676
(2007/10/03)
-
- Long-range intrinsic and equilibrium deuterium isotope effects on 19F chemical shifts
-
Deuterium isotope effects on 19F chemical shifts caused by deuteriation at OH or NH groups have been determined for intramolecularly hydrogen bonded compounds including fluorinated o-hydroxyacyl aromatics, enaminones, o-hydroxyazo and hydrazo compounds. The o-hydroxyazo and hydrazo compounds represent tautomeric and non-tautomeric cases. Deuterium isotope effects on fluorine chemical shifts for o-hydroxyacyl aromatics are found to parallel deuterium isotope effects at the carbon ipso to fluorine. For the azo and hydrazo compounds very long-range effects are seen formally over ten bonds. Throughspace effects are observed in the case of spatially close nuclei like 2-fluorobenzamide-N-α. The isotope effects on 19F chemical shifts can, in p-fluorophenyl substituted cases, be used to monitor the change in equilibrium upon deuteriation and therefore to estimate the importance of hydrogen bonds. Acta Chemica Scandinavica 1997.
- Hansen, Poul Erik,Bolvig, Simon,Buvari-Barcza, Agnes,Lycka, Antonin
-
p. 881 - 888
(2007/10/03)
-
- N-halogeno compounds. Part 18. 1-Alkyl-4-fluoro-1,4-diazoniabicyclo [2.2.2] octane salts: User-friendly site-selective electrophilic fluorinating agents of the N-fluoroammonium class
-
Methods of synthesis are described for a range of 1-alkyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane salts [R-N+(CH2CH2)3N+-F (X-)2, where R = CH3, CH2Cl, C2H5, CF3CH2, C8H17 and (X-)2 = (TfO-)2, (BF4-)2, (PF6-)2, (TfO-, BF4-), (TfO-, PF6-), (TfO-, FSO3-)] by direct fluorination (with neat F2 at ≤20 mmHg or F2-N2 blends at 1 atm pressure) of monoquaternary salts of 1,4-diazabicyclo[2.2.2]octane [R-+N(CH2CH2)3N X-] or their 1:1 adducts with boron trifluoride, phosphorus pentafluoride, or sulfur trioxide in acetonitrile at ca - 35°C. The results of site-selective electrophilic fluorination of diethyl sodio(phenyl)malonate [→ PhCF(CO2Et)2], 1-morpholinocyclohexene (→ 2-fluorocyclohexanone), phenol (→ 2- and 4-FC6H4OH), 1- and 2-hydroxynaphthalene (→ 2- and 4-FC10H6OH, and 1-FC10H6OH and 1,1-difluoro-2-oxo-1,2-dihydronaphthalene, respectively), acetanilide (→ 2- and 4-FC6H4NHCOCH3), anisole (→ 2- and 4-FC6H4OCH3) and sodium benzenesulfinate (→ PhSO2F) with these N-fluoroammonium salts are presented.
- Banks, R. Eric,Besheesh, Mohamed K.,Mohialdin-Khaffaf, Suad N.,Sharif, Iqbal
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p. 2069 - 2076
(2007/10/03)
-
- Photolysis of fluorodiphenylamines
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Photolysis of 2-fluoro-2′,5′-dimethyldiphenylamine 1a, in ethanol with a medium-pressure mercury lamp, gave a mixture of 1,4-dimethylcarbazole 7 (53%), 8-fluoro-1,4-dimethylcarbazole 2 (11%) and 6-ethoxy-2-fluoro-2′,5′-dimethyldiphenylamine 8 (19%). Photolysis of 4-fluoro-2′,5′-dimethyldiphenylamine 1b gave 6-fluoro-1,4-dimethylcarbazole 25 (35%) and 1,4-dimethylcarbazole 7 (47%).
- Groundwater, Paul W.,Hughes, David,Hursthouse, Michael B.,Lewis, Rhiannon
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p. 669 - 673
(2007/10/03)
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- Preparation and alkylation of regioisomeric tetrahydrophthalimide-substituted indolin-2(3H)-ones
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A series of novel regioisomeric tetrahydrophthalimide-substituted indolin-2-ones has been prepared via the Sommelet-Hauser type cyclization of appropriately substituted anilines as potential herbicides. The resultant indolin-2-ones were then regioselectively alkylated at N-1 and C-3 to give 1,3,3-trisubstituted indolin-2-ones. The most active series was also prepared by the bis-nitration of m-fluorophenylacetic acid followed by reduction and cyclization to give 6-amino-5-fluoroindolin-2-one. Elaboration to the tetrahydrophthalimide-substituted indolin-2-one was followed by C- and N-alkylation to give the desired compounds.
- Karp,Condon
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p. 1513 - 1520
(2007/10/02)
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- 1-Alkyl-4-fluoro-1,4-diazoniabicyclooctane Salts: a Novel Family of Electrophilic Fluorinating Agents
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Members of a new series of solid, easily handled, storable, transportable, commercially viable, site-selective electrophilic fluorinating agents of the +N-F class (tradenamed Selectfluor reagents) have been synthesized via direct fluorination of monoquaternary salts of 1,4-diazabicyclooctane.
- Banks, R. Eric,Mohialdin-Khaffaf, Suad N.,Lai, G. Sankar,Sharif, Iqbal,Syvret, Robert G.
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p. 595 - 596
(2007/10/02)
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- Kinetics of aminolysis of 2,4-dinitrophenyl acetate
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The second order rate constants for the reaction of 2,4-dinitrophenyl acetate with aniline and p- and o-substituted anilines have been reported in 10percent acetonitrile-90percent water (v/v) mixture at 25 deg, 30 deg, 35 deg and 40 deg C.In the reaction of p-substituted anilines, electron-releasing groups facilitate the reaction while electron-withdrawing groups retard it.The p-value is evaluated to be -2.33 +/- 0.16.The Broensted plot is also linear with βN = 0.792 +/- 0.027 at 30 deg C.The ΔS values are all negative as expected for bimolecular nucleophilic substitution reactions.In the case of o-substituted anilines, the rate data have been analyzed in terms of electronic and steric effects.
- Shunmugasundaram, A.,Thanulingam, T. Lekshmana,Ponnukalai, M.
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p. 757 - 760
(2007/10/02)
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- Power and structure-variable fluorinating agents. The N-fluoropyridinium salt system
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The usefulness of the N-fluoropyridinium salt system as a source of fluorinating agents was examined by using substituted or unsubstituted N-fluoropyridinium triflates 1-11, N-fluoropyridinium salts possessing other counteranions 1a-d and 3a, and the counteranion-bound salts, N-fluoropyridinium-2-sulfonates 12 and 13. Electrophilic fluorinating power was found to vary remarkably according to the electronic nature of the ring substituents. This power increased as the electron density of positive nitrogen sites decreased, and this was correlated to the pKa values of the corresponding pyridines. By virtue of this variation, it was possible to fluorinate a wide range of nucleophilic substrates differing in reactivity. It is thus possible to fluorinate aromatics, carbanions, active methylene compounds, enol alkyl or silyl ethers, vinyl acetates, ketene silyl acetals, and olefins through the proper use of salts pentachloro 6 through 2,4,6-trimethyl 2, their power decreasing in this order. All the reactions could be explained on the basis of a one-electron-transfer mechanism. N-Fluoropyridinium salts showed high chemoselectivity in fluorination, the extent depending on the reactive moiety. In consideration of these Findings, selective 9α-fluorination of steroids was carried out by reacting 1 with tris(trimethylsilyl ether) 73 of a triketo steroid. Regio- or stereoselectivity in fluorination was determined by a N-fluoropyridinium salt structure. Steric bulkiness of the N-F surroundings hindered the ortho fluorination of phenols and aniline derivatives, while the capacity for hydrogen bonding on the part of the counteranions prompted this process, and the counteranion-bound salts 12 and 13 underwent this fluorination exclusively or almost so. Both bulky N-fluoropyridinium triflates 2 and 7 preferentially attacked the 6-position of the conjugated vinyl ester of a steroid from the unhindered β-direction to give a thermally unstable 6β-fluoro isomer. On the basis of these results, N-fluoropyridinium salts may be concluded to constitute a system that can serve as a source of the most ideal fluorinating agents for conducting desired selective fluorination through fluorinating capacity or structural alteration.
- Umemoto, Teruo,Fukami, Shinji,Tomizawa, Ginjiro,Harasawa, Kikuko,Kawada, Kosuke,Tomita, Kyoichi
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p. 8563 - 8575
(2007/10/02)
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- Sterically Hindered N-Aryl-2(1H)-Quinolones and N-Aryl-6(5H)-Phenanthridinones: Separation of Enantiomers and Barriers to Racemization
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The novel N-aryl-4-chloro-3-methyl-2(1H)-quinolones (1)-(4) have been synthesized by condensation of the appropriate diphenylamine with diethyl methylmalonate and subsequent chlorination of the resulting N-aryl-4-hydroxy-3-methyl-2(1H)-quinolones (7)-(10). 5-(1-Naphthyl)-6(5H)-phenanthridinone (5) has been synthesized by the Chapman rearrangement of the 6-(1-naphthoxy)phenanthridine (11).Separation of the enantiomers (M) and (P) of the quinolones (1)-(4) and phenanthridinones (5), (6) was achieved by liquid chromatography on triacetylcellulose.The barriers to partial rotation about the C-N bond in (1)-(6) were determined by thermal racemization of enantiomers and are compared with those of structurally related molecules.
- Mintas, Mhaden,Mihaljevic, Vesna,Koller, Helmut,Schuster, Doris,Mannschreck, Albrecht
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p. 619 - 624
(2007/10/02)
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- HETEROCYCLIC SYSTEMS CONTAINING BRIDGEHEAD NITROGEN ATOM: PART LXVI. STUDIES OF ORIENTATION OF CYCLIZATION IN THE SYNTHESIS OF 8-FLUOROTHIAZOLOBENZIMIDAZOL-3(2H)-ONE
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2-Fluoro-6-nitroaniline, obtained by nitration of 2-fluoroacetanilide, on reduction with Raney nickel and hydrazine hydrate followed by treatment of the resulting diamine with carbon disulphide in situ gives 4-fluorobenzimidazolyl-2-thione.This thione on condensation with chloroacetic acid gives 4-fluorobenzimidazol-2-thiolacetic acid which on cyclization with a mixture of acetic anhydride and pyridine furnished 8-fluorothiazolobenzimidazol-3(2H)-one as revealed by 1H-NMR spectroscopy.The condensation of 4-fluorobenzimidazolyl-2-thione with 1,2-dibromoethane yields 2,3-dihydro-8-fluorothiazolobenzimidazole and sym-bis-(4-fluorobenzimidazol-2-ylmercapto)ethane.
- Dahiya, Rajinder,Pujari, H. K.
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p. 245 - 256
(2007/10/02)
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- Synthesis and Isomeric Conversions of Several 2-Substituted 1,4-Dihydro-4-oxo-3-quinolinecarboxylic Acid Derivatives
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Ethyl ester derivatives of 6- and 8-substituted 2-methyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids have been synthesized by treatment of the diethyl ester of acetylmalonic acid with 2- or 4-substituted anilines.Condensation of these newly synthesized quinolinecarboxylic acid derivatives with 4-nitrobenzaldehyde resulted in the formation of 6- and 8-substituted 2--1,4-dihydro-4-oxo-3-quinolinecarboxylic acids and ethyl esters of 6- and 8-substituted 2--4-acetoxy-3-quinolinecarboxylic acids.The tautomeric and conformational transformations of these newly synthesized compounds have also been investigated, using IR, NMR, and UV spectroscopy.
- Kononov, L. I.,Veinberg, G. A.,Liepin'sh, E. E.,Dipan, I. V.,Sukhova, N. M.,Lukevits, E.
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p. 765 - 771
(2007/10/02)
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- Synthesis of Asymmetrically Substituted Aminohalogenobenzimidazoles
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2-Fluoroacetanilide (1) upon treatment with HNO3-H2SO4 at -5 to 0 deg C gave 6-fluoro-4-nitroacetanilide (3) whereas at -20 to -10 deg C the product was 6-fluoro-3,4-dinitroacetanilide (5).Although the formation of compound (5) could be accounted for by a conventional nitration mechanism, the fact that (3) could not be nitrated to give (5) and that (5) was formed at a lower temperature than was (3) suggested that the reaction might proceed via an ipso δ intermediate (2).Deacetylation of (5) followed by reduction and condensation with formic acid in the presence of HCl gave 6(5)-fluoro-5(6)-formylaminobenzimidazole (11), 5(6)-amino-6(5)-fluorobenzimidazole (12) and 5-amino-4-chloro-6-fluorobenzimidazole (13).Reduction of (5) with tin followed by condensation with acetic acid gave 5(6)-amino-6(5)-fluoro-2-methylbenzimidazole (14).Concomitant reduction and cyclisation of 6-chloro-2,4-dinitroaniline with formic acid and HCl gave a mixture of 7(4)-chloro-5(6)-formylaminobenzimidazole (15) and 5-amino-4,7-dichlorobenzimidazole (16).
- Camarasa, Maria-Jose,Coe, Paul L.,Jones, A. Stanley,Walker, Richard T.
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p. 2317 - 2320
(2007/10/02)
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- Fluorination of Aromatic Derivatives with Fluoroxytrifluoromethane and Bis(fluoroxy)difluoromethane
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Fluoroxytrifluoromethane (CF3OF) and bis(fluoroxy)difluoromethane CF2(OF)2 are formed by the reaction of F2 with CO and CO2, respectively, over a CsF catalyst in a continouous-stream process.Both reagents react with aromatic substrates by an electrophilic substitution mechanism to yield fluoro-substituted derivatives.Fluorobenzene is produced in good yield from benzene, and aniline derivatives afford monofluorination products.Acetanilide (1), N-phenylmethanesulfonamide (2), α,α,α-trifluoroacetanilide (3), and 1,1,1-trifluoro(N-phenyl)methanesulfonamide (4) react with either reagent to yield mixtures of o- and p-fluoro-substituted derivatives.Solvent effects and competitive rate experiments demonstrate a preference for ortho substitution, especially in aprotic, nonpolar solvents.With particular substrates, these fluorinating agents are of practical synthetic utility, e.g., 2-fluoro-4-(trifluoromethyl)aniline is produced in high yield by fluorinating the intermediate 4-(trifluoromethyl)acetanilide (6) with CF3OF.Activated substrates such as toluene, xylenes, anisole, and cresols give mixtures of products which reduce the synthetic utility of these reagents.Nitrobenzene is fairly unreactive toward CF3OF and gives low yields of substitution products.
- Fifolt, Michael J.,Olczak, Raymond T.,Mundhenke, Rudolph F.
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p. 4576 - 4582
(2007/10/02)
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- A Novel Electrophilic Fluorination of Activated Aromatic Rings Using Acetyl Hypofluorite, Suitable also for Introducing (18)F into Benzene Nuclei
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Acetyl hypofluorite (1) is a new compound that serves as a novel electrophilic fluorinating agent.It is special in the sense that, while it is very reactive, it is still a milder reagent than other fluoroxy compounds such as CF3OF or CF3COOF.It is synthesized directly from elemental fluorine and is used without any isolation or purification.The hypofluorite 1 reacts efficiently and selectively with activated aromatic rings,particularly phenol and aniline derivatives after suitable protection of the hydroxyl and the amino groups.The net result of the reaction is partly according to classical aromatic electrophilic substitution.Unlike such a substitution, however, the electrophilic fluorine atom of 1 substitutes mainly an ortho hydrogen and only occasionally small amounts of p-fluoro derivatives are found.Evidence supports the mechanism for this aromatic fluorination as being mainly an addition-elimination one.In many cases the electrophilic aromatic fluorinations can replace the classical 60-year-old Balz-Schiemann method, which until today is probably the most used procedure.Since aromatic fluorination with 1 is a very fast reaction and since 1 is produced directly from elemental fluorine, this is probably one of the best ways for introduction of the short-living radioisotope (18)F into activated aromatic rings.This will greatly encourage the synthesis of compounds suitable for use in the rapidly developing field of positron emitting transaxial tomography, which in itself depends on the efficient and easy supply of compounds possessing positron emitting isotopes.
- Lerman, Ori,Yitzhak, Tor,Hebel, David,Rozen, Shlomo
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p. 806 - 813
(2007/10/02)
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- Reaction of Acetyl Hypofluorite with Aromatic Mercury Compounds: a New Selective Fluorination Method
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Aromatic fluorine compounds are prepared in acetic acid from the corresponding mercury compounds and acetyl hypofluorite.
- Visser, Gerard W. M.,Halteren, Bert W. v.,Herscheid, Jacobus D. M.,Brinkman, Gerard A.,Hoekstra, Arend
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p. 655 - 656
(2007/10/02)
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- Acetyl Hypofluorite as a Taming Carrier of Elemental Fluorine for Novel Electrophilic Fluorination of Activated Aromatic Rings
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The new fluorinating reagent CH3COOF, which is prepared in situ from F2, is used for electrophilic aromatic fluorinations of activated aromatic rings.
- Lerman, Ori,Tor, Yitzhak,Rozen, Shlomo
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p. 4629 - 4631
(2007/10/02)
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