- Alkylation of 5-Substituted 1 H-Tetrazoles via the Diazotization of Aliphatic Amines
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A new alkylation reaction of monosubstituted tetrazoles via the diazotization of aliphatic amines is reported. This method enables preferential formation of 2,5-disubstituted tetrazoles. A one-pot 1,3-dipolar cycloaddition/diazotization sequence starting from widely available nitriles is also described. Azide residues are quenched in the second step with the nitrite reagent, thus limiting the intrinsic risk associated with trimethylsilyl azide. The reaction conditions were compatible with several functional groups, including thiocyanates, which afford preferentially disubstituted 2-alkyl-5-(substituted-thio)tetrazoles.
- Lebel, Hélène,Reynard, Guillaume
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p. 12452 - 12459
(2021/09/07)
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- Discovery of mercaptopropanamide-substituted aryl tetrazoles as new broad-spectrum metallo-β-lactamase inhibitors
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β-Lactam antibiotic resistance mediated by metallo-β-lactamases (MBL) has threatened global public health. There are currently no available inhibitors of MBLs for clinical use. We previously reported the ruthenium-catalyzed meta-selective C-H nitration synthesis method, leading to some meta-mercaptopropanamide substituted aryl tetrazoles as new potent MBL inhibitors. Here, we described the structure-activity relationship of meta- and ortho-mercaptopropanamide substituted aryl tetrazoles with clinically relevant MBLs. The resulting most potent compound 13a showed IC50 values of 0.044 μM, 0.396 μM and 0.71 μM against VIM-2, NDM-1 and IMP-1 MBL, respectively. Crystallographic analysis revealed that 13a chelated to active site zinc ions via the thiol group and interacted with the catalytically important residues Asn233 and Tyr67, providing further structural information for the development of thiol based MBL inhibitors. This journal is
- Yan, Yu-Hang,Chen, Jian,Zhan, Zhen,Yu, Zhu-Jun,Li, Gen,Guo, Li,Li, Guo-Bo,Wu, Yong,Zheng, Yongxiang
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p. 31377 - 31384
(2020/09/21)
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- Application of Photoclick Chemistry for the Synthesis of Pyrazoles via 1,3-Dipolar Cycloaddition between Alkynes and Nitrilimines Generated In Situ
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The photochemical extrusion of gaseous nitrogen from 2,5-disubstituted tetrazoles to generate reactive nitrilimines in situ represents an efficient and attractive way to form dipoles that can be used to provide useful chemicals via 1,3-dipolar cycloadditions. The concept of “photoclick chemistry” already inspired numerous researchers, who exploited photochemical processes involving alkenes for the synthesis of adducts or the functionalization of biocompatible materials. The approach requires bioorthogonality, ease of access to the starting materials and operational simplicity. We report herein our investigations toward a photoclick reaction involving 2,5-disubstituted tetrazoles and alkynes as the dipolarophile for the synthesis of pyrazole derivatives. In addition to the numerous reports recently published on the synthesis of pyrazoles, we wish to add to the list a photochemical procedure that represents a mild and atom-economical alternative. Moreover, considering that such nitrilimines precursors can be accessed in one step from inexpensive and abundant starting materials and given the commercial availability of a broad spectrum of alkynes, we examined the scope of the photoclick reaction with respect to reactive partners, enabling the synthesis of a library of useful heteroaromatics.
- Remy, Richard,Bochet, Christian G.
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p. 316 - 328
(2018/01/27)
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- Preparation of 5-Aryl-2-Alkyltetrazoles with Aromatic Aldehydes, Alkylhydrazine, Di-tert-butyl Azodicarboxylate, and [Bis(trifluoroacetoxy)iodo]benzene
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A variety of 5-aryl-2-methyltetrazoles and 5-aryl-2-benzyltetrazoles were directly prepared in good to moderate yields by the reaction of aromatic aldehydes with methylhydrazine and benzylhydrazine, followed by treatment with di-tert-butyl azodicarboxylate and [bis(trifluoroacetoxy)iodo]benzene in a mixture of dichloromethane and 2,2,2-trifluoroethanol at room temperature. The present method is a novel one-pot preparation of 5-aryl-2-methyltetrazoles and 5-aryl-2-benzyltetrazoles through a [2N + 2N] combination under transition metal-free and mild conditions.
- Imai, Taro,Harigae, Ryo,Moriyama, Katsuhiko,Togo, Hideo
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p. 3975 - 3980
(2016/05/24)
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- Transition-metal-free direct alkylation of aryl tetrazoles via intermolecular oxidative C-N formation
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A transition-metal-free synthetic approach for constructing alkylated aryl tetrazoles has been developed using n-Bu4NI as the catalyst and t-BuOOH as the oxidant. It involves the direct C-N bond formation through sp3 C-H activation. A wide range of benzylic C-H substrates (or alkyl ethers) and aryl tetrazoles undergo this reaction smoothly to deliver the corresponding products in good yields.
- Wang, Liang,Zhu, Kaiqiang,Chen, Qun,He, Mingyang
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supporting information
p. 11780 - 11786
(2015/02/19)
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- Highly efficient synthesis of 5-substituted 1H-tetrazoles catalyzed by Cu-Zn alloy nanopowder, conversion into 1,5- and 2,5-disubstituted tetrazoles, and synthesis and NMR studies of new tetrazolium ionic liquids
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A series of 5-substituted 1H-tetrazoles were synthesized through [3+2] cycloaddition reactions between nitriles RCN and NaN3 in the presence of Cu-Zn alloy nanopowder as catalyst. The 1,5-dibutyl, 1-butyl-5-hexyl, 2,5-dibutyl, and 2-butyl-5-hexyl derivatives were then used as building blocks to synthesize several novel tetrazolium ionic liquids (ILs) with EtSO 4-, OTf-, and NTf2- counterions. Whereas alkylation of the 2,5-dialkyltetrazoles selectively gave the N-4 alkylated onium salts, with the 1,5-dialkyl derivatives approximately 1:1 mixtures of two tetrazolium salts were formed by alkylation at N-3 and N-4. The triflate and ethyl sulfate salts are room-temperature ILs that are hydrophilic, whereas the NTf2 salts are low-melting ILs and are hydrophobic. The resulting tetrazolium-based ionic liquids were studied by various multinuclear and 2D NMR techniques including natural abundance 15N and 1H/15N correlations.
- Aridoss, Gopalakrishnan,Laali, Kenneth K.
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experimental part
p. 6343 - 6355
(2011/12/03)
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- A practical synthesis of benzyl esters and related derivatives
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The benzyl ester is one of the earliest and best known of the carboxyl protecting groups. Its advantages over the corresponding methyl or ethyl ester derivatives lie in its ease of removal under very mild conditions, such as catalytic hydrogenation. The classical Fischer esterification of carboxylic acids in benzyl alcohol is not as easy as the analogous reaction in methanol or ethanol, due to the higher degree of steric hindrance imposed by the bulkier benzyl group and the difficulties encountered in evaporating the excess of high boiling benzyl alcohol at temperatures that could lead to decomposition of the products. Alternative routes such as the substitution of the silver or sodium salts with benzyl bromide, or the use of phenyldiazomethane have been described, but these are not always suitable, and the last method is inapropriate on large scale because of the explosive nature of the reagent. Klemm, Hintze and Gercken have also proposed a milder method adapted from earlier work by Vowinkel which involves the use of N,N'- dicyclohexyl-O-benzylisourea (DBI), itself obtained from N,N'-dicyclohexyl- carbodiimide (DCC) and benzyl alcohol. Another original route to benzyl esters is based on the thermal decomposition of benzyldimethylanilinium salts of carboxylic acids in refluxing toluene. This method needed modification for the preparation of acid sensitive tryptophan benzyl ester. More recently, benzyl trichloroacetimidate was found to convert carboxylic acids into the corresponding benzyl esters under catalysis by a Lewis acid such as boron trifluoride. As a complement to these earlier procedures, we now describe a mild, efficient, and practical benzylation method based on some new aspects of the chemistry of xanthates.
- Faure-Tromeur, Melanie,Zard, Samir Z.
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p. 7301 - 7304
(2007/10/03)
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- Novel regioselective N-alkylations of 5-substituted-2H-tetrazoles
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Regioselective alkylation of 5-substituted-2H-tetrazoles 1 to 2-alkyl derivatives 3 was achieved via decarboxylative alkylation with alkyl cyanoformates. Lesser selectivity was observed with chloroformates.
- Prhavc,Kobe
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p. 1925 - 1928
(2007/10/02)
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