- Direct, Late-Stage Mono-N-arylation of Pentamidine: Method Development, Mechanistic Insight, and Expedient Access to Novel Antiparastitics against Diamidine-Resistant Parasites
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A selective mono-N-arylation strategy of amidines under Chan-Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan-Lam mono-N-arylation. The scope of the process is demonstrated, and then applied to access the first mono-N-arylated analogues of pentamidine. Sub-micromolar activity against kinetoplastid parasites was observed for several analogues with no cross-resistance in pentamidine and diminazene-resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono-N-arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono-N-arylated pentamidine series was confirmed by UV-melt measurements using AT-rich DNA. This work highlights the potential to use Chan-Lam mono-N-arylation to develop therapeutic leads against diamidine-resistant trypanosomiasis and leishmaniasis.
- Robertson, Jack,Ungogo, Marzuq A.,Aldfer, Mustafa M.,Lemgruber, Leandro,McWhinnie, Fergus S.,Bode, Bela E.,Jones, Katherine L.,Watson, Allan J. B.,de Koning, Harry P.,Burley, Glenn A.
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supporting information
p. 3396 - 3401
(2021/09/06)
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- A Convenient Synthesis of Amidines via Cycloaddition-Decarboxylation of Isocyanates and Nitrones
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A base-promoted reaction between isocyanates and nitrones has been described, allowing an access to a variety of important functionalized amidines under mild reaction conditions. This strategy provides a convenient, effective, and scalable approach for the direct assembly of amidine compounds from simple starting materials in excellent yields.
- Chen, Xinyi,Wu, Yijing,Zhang, Mei-Mei
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p. 1773 - 1778
(2020/06/08)
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- Access to Amidines and Arylbenzimidazoles: Zinc-Promoted Rearrangement of Oxime Acetates
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An efficient and straightforward zinc-promoted rearrangement of oxime acetates with arylamines for the synthesis of amidines has been developed under mild conditions. This process involves N?O/C?C bond cleavages and C?C/C?N bond formations. Various oxime
- Zhu, Zhongzhi,Cen, Jinghe,Tang, Xiaodong,Li, Jianxiao,Wu, Wanqing,Jiang, Huanfeng
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p. 2020 - 2031
(2018/04/09)
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- Solvent/oxidant-switchable synthesis of multisubstituted quinazolines and benzimidazoles via metal-free selective oxidative annulation of arylamidines
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A fast and simple divergent synthesis of multisubstituted quinazolines and benzimidazoles was developed from readily available amidines, via iodine(III)-promoted oxidative C(sp3)-C(sp2) and C(sp 2)-N bond formation in nonpolar and polar solvents, respectively. Further selective synthesis of quinazolines in polar solvent was realized by TEMPO-catalyzed sp3C-H/sp2C-H direct coupling of the amidine with K2S2O8 as the oxidant. No metal, base, or other additives were needed.
- Lin, Jian-Ping,Zhang, Feng-Hua,Long, Ya-Qiu
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supporting information
p. 2822 - 2825
(2014/06/23)
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- Diverse tandem cyclization reactions of o -cyanoanilines and diaryliodonium salts with copper catalyst for the construction of quinazolinimine and acridine scaffolds
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Two cyclization modes are realized to produce different nitrogen-containing heterocycles, i.e.; quinazolin-4(3H)-imines and acridines by assembling o-cyanoanilines and diaryliodonium salts via tandem reaction pathways.
- Pang, Xinlong,Chen, Chao,Su, Xiang,Li, Ming,Wen, Lirong
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supporting information
p. 6228 - 6231
(2015/01/09)
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- Nitrenic reactivity of diazirines
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Butyl 3-bromo-3H-diazirine-3-carboxylate (7) and 3-bromo-3-phenyl-3H- diazirine (17) exhibit nitrenic reactivity with phenylmagnesium bromide or tetrabutylammonium cyanide. The formation of several N,N′-disubstituted amidines is attributed to the intermediacy of 1-phenyl or 1-cyano-1H-diazirines possessing a singlet imidoylnitrene character at the N2 atom. Most notably, the reaction of 7 with PhMgBr in diethyl ether affords 2-hydroxy-2,2,N- triphenylacetamidine (9) and 2-methyl-5,5-diphenyl-4-phenylamino-2,5- dihydrooxazole (10) as products derived from nitrene insertion to the ether α-C-H bond.
- Kolá?ová, Petra,?molík, Václav,Linhart, Igor,Martínez, Ignacio álvarez,Martin?, Tomá?
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p. 6764 - 6767
(2013/11/19)
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- Highly active nano-MgO catalyzed, mild, and efficient synthesis of amidines via electrophilic activation of amides
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Nano-MgO catalyzed synthesis of amidine derivatives is developed under solvent-free reaction condition at 70 C. Reusability of the catalyst and shorter reaction time as well as high yields are the advantages of this procedure.
- Das, Vijay Kumar,Thakur, Ashim Jyoti
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p. 4164 - 4166
(2013/07/26)
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- High temperature vapor phase reactions of nitrogen trifluoride with benzylic substrates
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At temperatures around 400°C, nitrogen trifluoride (NF3) readily reacts with benzylic substrates. Products vary with the substrate, but are all the result of difluoroamination at the benzylic position. Toluene and ethylbenzene produce benzonitrile. Cumene produces α-methylstyrene. Diphenylmethane produces benzanilide. Little or no direct fluorination or radical dimerization is observed.
- Belter, Randolph K.
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experimental part
p. 318 - 322
(2011/06/26)
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- Efficient access to polysubstituted amidines, benzimidazoles and pyrimidines from amides
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Polysubstituted amidines, benzimidazoles and pyrimidines were synthesized via the electrophilic activation of amides with trifluoromethanesulfonic anhydride and 2-chloropyridine. The one-pot protocol is concise and efficient and the substrates are readily available.
- Wang, Jing,He, Zhenxing,Chen, Xiaopeng,Song, Wangze,Lu, Ping,Wang, Yanguang
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experimental part
p. 1208 - 1214
(2010/04/02)
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- Extraction-spectrophotometric determination of rhenium(VII) with thiocyanate and amidines in the presence of cetyltrimethylammonium bromide
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A simple and selective spectrophotometric method has been developed for the determination of rhenium(VII) in the ore sample based on the reaction of ReVII with thiocyanate in the presence of tin(II) chloride in sulfuric acid media and subsequent extraction of the complex with chloroform solution of N,N′-diphenylbenzamidine (DPBA) and its nine derivatives in the presence of a cationic surfactant, cetyltrimethylammonium bromide (CTAB). The effects of acids and organic solvents on the extraction of the metal and colour intensity of the complex are discussed. The tolerance limits of diverse ions are very high. MoVI interferes it but is removed by prior precipitation by oxine effectively. The molar absorptivity and detection limit of the method with DPBA are (3.65 ± 0.02) × 104 dm -3 mol-1 cm-1 and 0.004 μg ml-1, respectively. The relative standard deviation of the method at a level of 25 μg ReVII / 10 ml is ± 1.2%.
- Deb, Manas Kanti,Shrivastava, Mona
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p. 388 - 389
(2007/10/03)
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- Annulation Reactions with Iron(III) Chloride: Oxidation of Imines
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Aromatic imines react with phenylacetylene or styrene in an acetonitrile solution of iron(III) chloride to give quinolines 3 or their tetrahydro derivatives 11 together with variable amounts of products 4 arising from the reduction of the imines.The initial step appears to be a one-electron oxidation to generate iron(II) and an imine radical cation.When the reactions are carried out in the presence of stoichiometric amounts of tetrachloro-p-benzoquinone (chloranil), only quinolines 3 are obtained.
- Leardini, Rino,Nanni, Daniele,Tundo, Antonio,Zanardi, Giuseppe,Ruggieri, Fabrizio
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p. 1842 - 1848
(2007/10/02)
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- Reaction of N,N-Dimethyl-N'-thiobenzoylformamidine and N,N-Dimethyl-N'-phenylthiocarbamoylformamidine with N-Arylbenzimidoyl Chlorides
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The reactions of N,N-dimethyl-N'-thiobenzoylformamidine (1) and N,N-dimethyl-N'-phenylthiocarbamoylformamidine (4) with N-arylbenzimidoyl chlorides (2) have been studied.Compound 1 reacts with 2 in dry chloroform at room temperature to give dimidoyl sulphides (3) in good yields.However, the reaction of 2 with 4 in dry tetrahydrofuran under reflux results in the formation of a mixture of thiobenzanilides (5) and N-aryl-N'-phenylbenzamidines (6).Possible mechanistic pathways for these reactions have been suggested.
- Baruah, P. D.,Roy, G.,Satsangi, R.,Mahajan, M. P.
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p. 357 - 359
(2007/10/02)
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- Synthesis of Amides and Amidines by Reaction of Carboxylic Acids and Amines in the Presence of Polyphophoric Acid Trimethylsilyl Ester (PPSSE)
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The reaction between amines and carboxylic acids in the presence of poliphosphoric acid trimethylsilylester (PPSE) has been investigated from the view point of the synthesis of amides and amidines.Benzanilide was selectively prepared from benzoic acid and aniline in the presence of PPSE and pyridine at 100 degC, whereas a mixture of benzanilide and N,N'-diphenylbenzamidine was obtained without the use of pyridine.The reaction at 160 degC almost exclusively gave N,N'-diphenylbenzamidine.Various simmetrical amidines were obtained from combinations of carboxylic acids and aromatic amines in high yields by simply heating at 160 degC with four molar amounts of PPSE.The reactions of aliphatic and aromatic amines with N-monosubstituted and N,N-disubstituted amides also afforded corresponding unsymmetrical amidines under the same conditions.The reaction mechanism is discussed in some detail.
- Ogata, Shin-ichi,Mochizuki, Amane,Kakimoto, Masa-aki,Imai, Yoshio
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p. 2171 - 2178
(2007/10/02)
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- A NOVEL DIRECT SYNTHESIS OF AMIDINES FROM CARBOXYLIC ACIDS AND AMINES USING POLYPHOSPHORIC ACID TRIMETHYLSILYL ESTER (PPSE) AS CONDENSING AGENT
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It was found that amidines were obtained directly by the reaction of carboxylic acids with amines in the presence of PPSE, and the yields of amidines were dependent on the structure of amines rather than that of carboxylic acids.
- Kakimoto, Masa-aki,Ogata, Shin-ichi,Mochizuki, Amane,Imai, Yoshio
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p. 821 - 824
(2007/10/02)
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- Ketene. Part 21. Reactions of Heterocumulenes with Nitrones
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Degradative and mass spectrometric evidence confirms the formation of the isoxazolidinones (2) from the reaction of cyano-t-butylketene with the N-alkyl nitrones (1), whilst the reaction with the N-phenyl nitrone (1d) gives the expected oxazolidinone (3b).Cyano-t-butylketene reacts with diphenyl nitrone to give the indolones (10a) and (10b).The reaction of phenyl isocyanate with diphenyl nitrone, and the N-alkyl nitrones (1a) and (1d) gives the normal 1,3-dipolar cycloadducts without rearrangement.Ethoxycarbonyl-t-butylketene reacts with the N-phenyl nitrone (1d) to give an oxazolidinone , but reaction with the N-alkyl nitrones (1) gives only fluorenone azine.This ketene reacts with diphenyl nitrone to give the anil (15) and the dihydroindole (16).
- Evans, Andrew R.,Hafiz, Mushtaq,Taylor, Giles A.
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p. 1241 - 1246
(2007/10/02)
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- REACTIVITY OF N-SUBSTITUTED BENZIMIDOYL CHLORIDES WITH ANILINE IN BENZENE
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The kinetics of the reaction of N-substituted benzimidoyl chlorides C6H5C(Cl)=NR with aniline in benzene at 25 deg C were studied.The results were compared with the reactivity of benzoyl chloride C6H5C(Cl)=O and thiobenzoyl chloride C6H5C(Cl)=S.On the basis of the high sensitivity of the process to the introduction of a substituent R at the nitrogen atom in the imidoyl chloride molecule it is concluded that the C=N bond takes part as "reactant" in a nucleophilic substitution mechanism.
- Mikhailov, B. A.,Drizhd, L. P.,Litvinenko, L. M.,Bondarenko, L. I.,Savelova, V. A.
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p. 1309 - 1313
(2007/10/02)
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- Mesoionic Six-membered Heterocycles, III. - Reactions of o-Quinonoid Compounds with 6-Oxo-6H-1,3-diazin-1-ium-4-olates
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Mesoionic 6-oxo-6H-1,3-diazin-1-ium-4-olates 9 react with tetrachloro-o-benzoquinone (2, R=Cl) to give 1 : 1 adducts 12 which can formally be derived from ketene tautomers 13 of 9.The structure of 12f has been clarified by X-ray crystallography.
- Friedrichsen, Willy,Schmidt, Regine,Hummel, Gerrit J. van,Ham, Dirk M. W. van den
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p. 521 - 531
(2007/10/02)
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