- 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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- Synthesis of aminoisoquinolines via Rh-catalyzed [4 + 2] annulation of benzamidamides with vinylene carbonate
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A new strategy is developed for the synthesis of 1-aminoisoquinoline derivatives. This Rh(III)-catalyzed [4 + 2] annulation reaction employs benzamidines as efficient directing groups and the vinylene carbonate as an acetylene surrogate. Additionally, the reaction features broad substrate scopes and good yields, only producing carbonate anion as byproduct.
- Huang, Xin,Xu, Yingying,Li, Jianglian,Lai, Ruizhi,Luo, Yi,Wang, Qiantao,Yang, Zhongzhen,Wu, Yong
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supporting information
p. 3518 - 3521
(2021/06/12)
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- Transition-Metal-Free Synthesis of 1,2-diphenyl-1H-benzo[d] Imidazole Derivatives from N-phenylbenzimidamides and Cyclohexanones
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A transition-metal-free strategy for the formation of 1,2-diphenyl-1H-benzo[d] imidazoles from N-phenylbenzimidamides and cyclohexanones is introduced. This is the first report on the direct synthesis of 1,2-diphenyl-1H-benzo[d] imidazoles from cyclohexanones and N-phenylbenzimidamides via iodine- promoted oxidative cyclization. Non-aromatic cyclohexanones were smoothly dehydrogenated, and acted as an aryl source using oxygen as a green oxidant. The catalytic use of iodine makes this method quite simple, more economical and convenient. Under optimized conditions, various substituted 1,2-diphenyl-1H-benzo[d] imidazoles were smoothly reacted, and the desired substituted imidazoles were generated with moderate to excellent yields. (Figure presented.).
- Lu, Guoqiang,Luo, Nan,Hu, Fangpeng,Ban, Zihui,Zhan, Zhenzhen,Huang, Guo-Sheng
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supporting information
p. 487 - 492
(2019/12/12)
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- Synthesis of 1,2-dihydro-1,3,5-triazine derivativesviaCu(ii)-catalyzed C(sp3)-H activation ofN,N-dimethylethanolamine with amidines
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1,2-Dihydro-1,3,5-triazines and symmetrical 1,3,5-triazines were obtained in up to 81% yields from amidines andN,N-dimethylethanolamine catalyzed by CuCl2. The reaction involves three C-N bond formations during the oxidative annulation process
- Chen, Rener,Ma, Renchao,Ma, Yongmin,Wang, Lei,Wang, Zhiming,Yan, Min
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supporting information
p. 10946 - 10949
(2020/10/02)
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- Acid-catalyzed synthesis of imidazole derivatives via N-phenylbenzimidamides and sulfoxonium ylides cyclization
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A straightforward method to synthesize imidazole derivatives from amidines and sulfoxonium ylides catalyzed by acids is reported in this study. Specifically, catalyzed by trifluoroacetic acid in DCE solvents can improve synthesis efficiency under metal-fr
- Tian, Yuan,Qin, Mingda,Yang, Xueying,Zhang, Xueguo,Liu, Yafeng,Guo, Xin,Chen, Baohua
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supporting information
p. 2817 - 2823
(2019/04/13)
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- Metal-Free C-B Bond Cleavage: An Acid Catalyzed Three-Component Reaction Construction of Imidazole-Containing Triarylmethanes
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An efficient acid-catalyzed strategy to prepare imidazole-containing triarylmethanes from amidines, ynals, and boronic acids has been developed. It represents an unprecedented and novel metal-free C-B bond cleavage strategy as a workable route to form new carbon-carbon bonds.
- Wang, Changcheng,Yu, Yue,Su, Zhengquan,Li, Xuechen,Cao, Hua
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supporting information
p. 4420 - 4423
(2019/06/27)
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- Transition-metal-free three-component reaction: Additive controlled synthesis of sulfonylated imidazoles
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Two efficient transition-metal-free highly regioselective pathways for constructing sulfonylated imidazoles via three-component reactions of amidines, ynals, and sodium sulfonates have been developed. The generations of different sulfonylated imidazoles w
- Liu, Wei,Zhang, Yu,He, Jiaming,Yu, Yue,Yuan, Jiajun,Ye, Xiaoyi,Zhang, Ziwu,Xue, Liang,Cao, Hua
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p. 11348 - 11358
(2019/09/09)
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- Direct Synthesis of 3-Acylindoles through Rhodium(III)-Catalyzed Annulation of N-Phenylamidines with α-Cl Ketones
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In the present study, a novel synthetic strategy to directly produce versatile 3-acylindoles through Rh(III)-catalyzed C-H activation and annulation cascade of N-phenylamidines with α-Cl ketones was developed, in which α-Cl ketones serve as unusual one-carbon (sp3) synthons. This strategy features high regioselectivity, efficiency, wide substrate tolerance, and mild reaction conditions, which further underscore its synthetic utility in drug molecule synthesis.
- Zhou, Jianhui,Li, Jian,Li, Yazhou,Wu, Chenglin,He, Guoxue,Yang, Qiaolan,Zhou, Yu,Liu, Hong
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supporting information
p. 7645 - 7649
(2018/12/11)
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- Unaromatized Tetrahydrobenzimidazole Synthesis from p-Benzoquinone and N-Arylamidines and their Cytotoxic Potential
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A diverse set of unaromatized and densely functionalized tetrahydrobenzimidazole adducts were obtained in good yields by simple mixing p-benzoquinone 1 with N-arylamidines 2 under mild conditions. The main features of these adducts include a hemi N,O-acet
- Tran, Minh Quan,Nguyen, Thanh Binh,Sawadogo, Wamtinga Richard,Ermolenko, Ludmila,Song, Sungmi,Retailleau, Pascal,Diederich, Marc,Al-Mourabit, Ali
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supporting information
p. 5878 - 5884
(2018/10/09)
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- N-Heterocyclic carbene-catalyzed annulation of ynals with amidines: Access to 1,2,6-trisubstituted pyrimidin-4-ones
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An N-heterocyclic carbene-catalyzed annulation of ynals and amidines has been reported to construct pyrimidin-4-ones. The protocol features a broad substrate scope and mild conditions. Furthermore, an oxidative strategy to catalytically generate ynal-deri
- Xie, Yangxi,Wang, Jian
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p. 4597 - 4600
(2018/05/14)
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- Copper-Catalyzed Intramolecular C-H Amination: A New Entry to Substituted Xanthine Derivatives
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Catalytic synthesis of xanthines was achieved in the presence of a copper catalyst. The process involves copper-catalyzed intramolecular C-H amination of benzamidines that possess a uracil moiety and produces variously substituted xanthines generally in good to high yields. This work introduces a new, facile approach to polysubstituted xanthine compounds..
- Shimizu, Maki,Hayama, Noboru,Kimachi, Tetsutaro,Inamoto, Kiyofumi
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p. 4183 - 4190
(2017/09/12)
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- Silver-catalyzed [3 + 2] domino reaction: An efficient strategy to synthesize imidazole-5-carbaldehydes
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An unprecedented regioselective silver-catalyzed [3 + 2] domino reaction of amidines and ynals for the formation of C-N bonds has been developed. The reaction provided a new route to prepare imidazole-5-carbaldehydes which are important intermediates for the construction of fine chemicals. The reaction proceeds smoothly with a broad range of substrates to give imidazoles in good yields.
- Wang, Changcheng,Jiang, Hangqi,Chen, Weifeng,Dong, Jun,Chen, Zhengwang,Cao, Hua
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supporting information
p. 6463 - 6466
(2017/08/16)
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- Substrate-Controlled Selectivity Switch in a Three-Component Reaction: A Ag-Catalyzed Strategy for the Synthesis of Functionalized Imidazoles
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An efficient Ag-catalyzed three-component reaction of amidines, ynals, and alcohols, phenols, or water has been developed. This strategy provides a wide range of substrates and represents a simple process for the preparation of different imidazole derivatives in good yields with high regioselectivities.
- Wang, Changcheng,Wang, Enming,Chen, Weixin,Zhang, Lijuan,Zhan, Haiying,Wu, Yuanheng,Cao, Hua
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p. 9144 - 9153
(2017/09/11)
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- Iodine-Mediated Aryl C?H Amination for the Synthesis of Benzimidazoles and Pyrido[1,2-a]benzimidazoles
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An intramolecular aryl C?H amination reaction has been achieved using molecular iodine as the sole oxidant for the synthesis of benzimidazole derivatives. The required substrates were readily prepared by addition or coupling of arylamines with the corresponding nitriles or aryl iodides. Iodine-mediated oxidative cyclization of these substrates in the presence of potassium carbonate (K2CO3) as base afforded the corresponding products in moderate to good yields. The transition metal-free protocol presented here is insensitive to air and operationally simple. This versatile and eco-friendly synthetic methodology is broadly applicable to a variety of N-aryl-substituted amidines and pyridin-2-amines, and provides direct access to both 1H-benzo[d]imidazole and pyrido[1,2-a]benzimidazole derivatives from the corresponding precursors. (Figure presented.).
- Lv, Zhigang,Liu, Jing,Wei, Wei,Wu, Jie,Yu, Wenquan,Chang, Junbiao
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supporting information
p. 2759 - 2766
(2016/09/13)
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- Copper-catalyzed oxidative diamination of terminal alkynes by amidines: Synthesis of 1,2,4-trisubstituted imidazoles
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An efficient copper-catalyzed synthesis of 1,2,4-trisubstituted imidazoles using amidines and terminal alkynes has been developed. Overall, the oxidative process, which involves Na2CO3, pyridine, a catalytic amount of CuCl2/sub
- Li, Jihui,Neuville, Luc
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supporting information
p. 1752 - 1755
(2013/06/26)
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- C-H cycloamination of N-aryl-2-aminopyridines and N-arylamidines catalyzed by an in situ generated hypervalent iodine(iii) reagent
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A metal-free synthesis of diversified pyrido[1,2-a]benzimidazoles and 1H-benzo[d]imidazoles from N-aryl-2-aminopyridines and N-arylamidines has been developed. The C-H cycloamination reaction was catalyzed by hypervalent iodine(iii) species generated in situ from iodobenzene (catalytic) and peracetic acid (stoichiometric). The reaction proceeded smoothly at ambient temperature to provide the corresponding N-heterocycles in good to excellent yields.
- He, Yimiao,Huang, Jinbo,Liang, Dongdong,Liu, Lanying,Zhu, Qiang
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supporting information
p. 7352 - 7354
(2013/09/23)
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- Synthesis and structure of aroylamidines and N-arylbenzamidines hydrochlorides
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Aroylamidines can be obtained as salts in a reaction of the corresponding arylcarbonitriles with anhydrous ethanol in the presence of dry HCl followed by treating intermediate imidoesters with alcoholic solution of ammonia. N-Arylbenzamidines are obtained by reacting benzonitrile with arylamines in the presence of AlCl3. The structure of arylamines and the reaction conditions signifi cantly affect the yield of the target product, and sometimes the very possibility of its preparation. Pleiades Publishing, Ltd., 2012.
- Kuvaeva,Fedorova,Zaitsev,Yakovlev,Zakharov,Semakova
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experimental part
p. 209 - 213
(2012/06/01)
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- Synthesis of benzimidazoles by PIDA-promoted direct C(sp2)-H imidation of N-arylamidines
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A metal-free synthesis of diversified benzimidazoles from N-arylamidines through a phenyliodine(III) diacetate (PIDA) promoted intramolecular direct C(sp2)-H imidation has been developed. The reaction proceeds smoothly at 0 °C or ambient temperature to provide the desired products in good to excellent yields. The synthesis of 2-alkyl- or 2-alkyl-fused benzimidazoles, which are generally inaccessible by similar Pd- or Cu-catalyzed approaches, can also be achieved. Copyright
- Huang, Jinbo,He, Yimiao,Wang, Yong,Zhu, Qiang
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supporting information
p. 13964 - 13967
(2013/01/15)
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- Ligand-free copper-catalyzed arylation of amidines
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Copper-catalyzed cross-coupling reactions of amidine salts were utilized to synthesize monoarylated amidines in moderate to high yields with ligand-free conditions. DMF was the superior solvent for the N-arylation of benzamidines, while MeCN was used in the formation of N-aryl amidines in moderate to high yield.(Figure Presented)
- Cortes-Salva, Michelle,Garvin, Corey,Antilla, Jon C.
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supporting information; experimental part
p. 1456 - 1459
(2011/04/26)
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- Palladium-catalyzed intramolecular C(sp2)-H amidination by isonitrile insertion provides direct access to 4-aminoquinazolines from N-arylamidines
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An efficient method for the synthesis of 4-amino-2-aryl(alkyl)quinazolines from readily available N-arylamidines and isonitriles via palladium-catalyzed intramolecular aryl C-H amidination by isonitrile insertion has been developed.
- Wang, Yong,Wang, Honggen,Peng, Jiangling,Zhu, Qiang
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supporting information; experimental part
p. 4604 - 4607
(2011/10/12)
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- Direct imidation to construct 1H-benzo[d]imidazole through Pd II-catalyzed C-H activation promoted by thiourea
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A study was conducted to demonstrate the development of a method to construct 1H-benzo[d]immidazole through PdII -catalyzed intermolecular C-H activation starting from N-phenylbenziimidamide. The detailed mechanism investigations indicated that a palladacycle monomer or dimer was the key intermediate for this transformation, demonstrating that thiourea was first used to influence the efficiency of C-H activation. The method was found to construct 1H-benzo[d]immidazole through PdII -catalyzed intermolecular C-H activation extending the substrate scope widely. It also demonstrated the introduction of thiourea (tetramethylthiourea) (TMTU) for the first time as an additive to promote the efficiency of PdII catalysis for the direct C-H transformation. N-phenylbenziimidamide was also readily synthesized through the addition of aniline to benzonitrile according to the method to conduct the investigations.
- Xiao, Qing,Wang, Wen-Hua,Liu, Gang,Meng, Fan-Ke,Chen, Jia-Hua,Yang, Zhen,Shi, Zhang-Jie
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supporting information; experimental part
p. 7292 - 7296
(2010/03/24)
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- Samarium diiodide induced reductive coupling of nitriles with azides
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A series of amidine derivatives were synthesized via the intermolecular reductive coupling of nitriles with azides induced by samarium diiodide in good yields under mild and neutral conditions.
- Su,Li,Zhang
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- Synthesis & Pharmacological Evaluation of Ethyl 3-Substituted-phenyl-2-methylmercapto/ phenyl/ methyl-4(3H)-pyrimidone-5-carboxylates
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A number of ethyl 3-substituted-phenyl-2-methylmercapto/ phenyl/ methyl-4(3H)-pyrimidone-5-carboxylates (V) have been prepared by the reaction of amidines (III) with diethyl ethoxymethylenemalonate.In order to confirm the structure (V), ethyl 3-(2'-methylphenyl)-2-methylmercapto-4(3H)pyrimidone-5-carboxylate (103) has been transformed into the earlier synthesised 3-(2'-methylphenyl)-2-methylmercapto-4(3H)-pyrimidone (115) by decarboxylation of 3-(2'-methylphenyl)-2-methylmercapto-4(3H)-pyrimidone-5-carboxylic acid (114), obtained by the alkaline hydrolysis of 103.Someof these compounds have shown antiinflammatory, diuretic and antipassive cutaneous anaphylaxis activities.
- Gupta, K. A.,Saxena, Anil K.,Jain, Padam C.
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p. 228 - 233
(2007/10/02)
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- The synthesis, analysis, stability and biotransformation of N-(3-methylphenyl)-N'-cyanobenzamidine and analogues (author's transl)
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The antivirally active N-(3-methylphenyl)-N'-cyanobenzamidine (1) and some of its analogues were synthetized by the reaction of the ethyl ester of N-cyanobenzimidic acid with the corresponding arylamines. The analytical profile of 1 and of some of its analogues, which is needed for stability and biotransformation studies, was established by means of the following techniques: solubility determination, TLC, UV, IR and MS. When 1 is heated with methanolic HCl and NaOH (0.5 mol/l) for 1 h, several hydrolysis products are formed: m-toluidine, benzoic acid, benzoic acid 3-toluidide, N-(3-methylphenyl)benzamidine, N-(3-methylphenyl)-N'-carboxamidobenzamidine, benzoylurea, However, 1 is fairly stable under physiological conditions so biotransformation studies are not affected. After oral application of 1 to rats, the 3-hydroxymethyl and the 3-methyl-5-hydroxy compound as well as its glucuronide and sulphate conjugate were detected in the urine. The faeces contained considerable amounts of unchanged 1 (incomplete absorption).
- Pfeifer,Barnikow,Schulz,Kraft,Fritsche
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p. 757 - 763
(2007/10/02)
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